To see the other types of publications on this topic, follow the link: Vertebrates Wnt genes.
Journal articles on the topic 'Vertebrates Wnt genes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Vertebrates Wnt genes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Holland, Peter W. H., Jordi Garcia-Fernàndez, Nic A. Williams, and Arend Sidow. "Gene duplications and the origins of vertebrate development." Development 1994, Supplement (January 1, 1994): 125–33. http://dx.doi.org/10.1242/dev.1994.supplement.125.
Full textAbstract:
All vertebrates possess anatomical features not seen in their closest living relatives, the protochordates (tunicates and amphioxus). Some of these features depend on developmental processes or cellular behaviours that are again unique to vertebrates. We are interested in the genetic changes that may have permitted the origin of these innovations. Gene duplication, followed by functional divergence of new genes, may be one class of mutation that permits major evolutionary change. Here we examine the hypothesis that gene duplication events occurred close to the origin and early radiation of the vertebrates. Genome size comparisons are compatible with the occurrence of duplications close to vertebrate origins; more precise insight comes from cloning and phylogenetic analysis of gene families from amphioxus, tunicates and vertebrates. Comparisons of Hox gene clusters, other homeobox gene families, Wnt genes and insulin-related genes all indicate that there was a major phase of gene duplication close to vertebrate origins, after divergence from the amphioxus lineage; we suggest there was probably a second phase of duplication close to jawed vertebrate origins. From amphioxus and vertebrate homeobox gene expression patterns, we suggest that there are multiple routes by which new genes arising from gene duplication acquire new functions and permit the evolution of developmental innovations.
2
Parr, B. A., M. J. Shea, G. Vassileva, and A. P. McMahon. "Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds." Development 119, no. 1 (September 1, 1993): 247–61. http://dx.doi.org/10.1242/dev.119.1.247.
Full textAbstract:
Mutation and expression studies have implicated the Wnt gene family in early developmental decision making in vertebrates and flies. In a detailed comparative analysis, we have used in situ hybridization of 8.0- to 9.5-day mouse embryos to characterize expression of all ten published Wnt genes in the central nervous system (CNS) and limb buds. Seven of the family members show restricted expression patterns in the brain. At least three genes (Wnt-3, Wnt-3a, and Wnt-7b) exhibit sharp boundaries of expression in the forebrain that may predict subdivisions of the region later in development. In the spinal cord, Wnt-1, Wnt-3, and Wnt-3a are expressed dorsally, Wnt-5a, Wnt-7a, and Wnt-7b more ventrally, and Wnt-4 both dorsally and in the floor plate. In the forelimb primordia, Wnt-3, Wnt-4, Wnt-6 and Wnt-7b are expressed fairly uniformly throughout the limb ectoderm. Wnt-5a RNA is distributed in a proximal to distal gradient through the limb mesenchyme and ectoderm. Along the limb's dorsal-ventral axis, Wnt-5a is expressed in the ventral ectoderm and Wnt-7a in the dorsal ectoderm. We discuss the significance of these patterns of restricted and partially overlapping domains of expression with respect to the putative function of Wnt signalling in early CNS and limb development.
3
Ansari, Salim, Nicole Troelenberg, Van Anh Dao, Tobias Richter, Gregor Bucher, and Martin Klingler. "Double abdomen in a short-germ insect: Zygotic control of axis formation revealed in the beetle Tribolium castaneum." Proceedings of the National Academy of Sciences 115, no. 8 (February 5, 2018): 1819–24. http://dx.doi.org/10.1073/pnas.1716512115.
Full textAbstract:
The distinction of anterior versus posterior is a crucial first step in animal embryogenesis. In the fly Drosophila, this axis is established by morphogenetic gradients contributed by the mother that regulate zygotic target genes. This principle has been considered to hold true for insects in general but is fundamentally different from vertebrates, where zygotic genes and Wnt signaling are required. We investigated symmetry breaking in the beetle Tribolium castaneum, which among insects represents the more ancestral short-germ embryogenesis. We found that maternal Tc-germ cell-less is required for anterior localization of maternal Tc-axin, which represses Wnt signaling and promotes expression of anterior zygotic genes. Both RNAi targeting Tc-germ cell-less or double RNAi knocking down the zygotic genes Tc-homeobrain and Tc-zen1 led to the formation of a second growth zone at the anterior, which resulted in double-abdomen phenotypes. Conversely, interfering with two posterior factors, Tc-caudal and Wnt, caused double-anterior phenotypes. These findings reveal that maternal and zygotic mechanisms, including Wnt signaling, are required for establishing embryo polarity and induce the segmentation clock in a short-germ insect.
4
Kudoh, Tetsuhiro, Stephen W. Wilson, and Igor B. Dawid. "Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm." Development 129, no. 18 (September 15, 2002): 4335–46. http://dx.doi.org/10.1242/dev.129.18.4335.
Full textAbstract:
Early neural patterning in vertebrates involves signals that inhibit anterior (A) and promote posterior (P) positional values within the nascent neural plate. In this study, we have investigated the contributions of, and interactions between, retinoic acid (RA), Fgf and Wnt signals in the promotion of posterior fates in the ectoderm. We analyze expression and function of cyp26/P450RAI, a gene that encodes retinoic acid 4-hydroxylase, as a tool for investigating these events. Cyp26 is first expressed in the presumptive anterior neural ectoderm and the blastoderm margin at the late blastula. When the posterior neural gene hoxb1b is expressed during gastrulation, it shows a strikingly complementary pattern to cyp26. Using these two genes, as well as otx2 and meis3 as anterior and posterior markers, we show that Fgf and Wnt signals suppress expression of anterior genes, including cyp26. Overexpression of cyp26 suppresses posterior genes, suggesting that the anterior expression of cyp26 is important for restricting the expression of posterior genes. Consistent with this, knock-down of cyp26 by morpholino oligonucleotides leads to the anterior expansion of posterior genes. We further show that Fgf- and Wnt-dependent activation of posterior genes is mediated by RA, whereas suppression of anterior genes does not depend on RA signaling. Fgf and Wnt signals suppress cyp26 expression, while Cyp26 suppresses the RA signal. Thus, cyp26 has an important role in linking the Fgf, Wnt and RA signals to regulate AP patterning of the neural ectoderm in the late blastula to gastrula embryo in zebrafish.
5
Ziemer, Lisa Taneyhill, Diane Pennica, and Arnold J. Levine. "Identification of a Mouse Homolog of the Human BTEB2Transcription Factor as a β-Catenin-Independent Wnt-1-Responsive Gene." Molecular and Cellular Biology 21, no. 2 (January 15, 2001): 562–74. http://dx.doi.org/10.1128/mcb.21.2.562-574.2001.
Full textAbstract:
ABSTRACT The Wnt/Wg signaling pathway functions during development to regulate cell fate determination and patterning in various organisms. Two pathways are reported to lie downstream of Wnt signaling in vertebrates. The canonical pathway relies on the activation of target genes through the β-catenin–Lef/TCF complex, while the noncanonical pathway employs the activation of protein kinase C (PKC) and increases in intracellular calcium to induce target gene expression. cDNA subtractive hybridization between a cell line that overexpresses Wnt-1 (C57MG/Wnt-1) and the parental cell line (C57MG) was performed to identify downstream target genes of Wnt-1 signaling. Among the putative Wnt-1 target genes, we have identified a mouse homolog of the gene encoding human transcription factor basic transcription element binding protein 2 (mBTEB2). ThemBTEB2 transcript is found at high levels in mammary tissue taken from a transgenic mouse overexpressing Wnt-1 (both tissue prior to active proliferation and tumor tissue) but is barely detectable in wild-type mouse mammary glands. The regulation of mBTEB2 by Wnt-1 signaling in tissue culture occurs through a β-catenin–Lef/TCF-independent mechanism, as it is instead partially regulated by PKC. The Wnt-1-induced, PKC-dependent activation of mouse BTEB2 in C57MG cells, as well as the ability of Wnt-1 to stabilize β-catenin in these cells, is consistent with the hypothesis that both the noncanonical and canonical Wnt pathways are activated concomitantly in the same cell. These results suggest that mBTEB2 is a biologically relevant target of Wnt-1 signaling that is activated through a β-catenin-independent, PKC-sensitive pathway in response to Wnt-1.
6
Taneyhill, Lisa A., and Marianne Bronner-Fraser. "Dynamic Alterations in Gene Expression after Wnt-mediated Induction of Avian Neural Crest." Molecular Biology of the Cell 16, no. 11 (November 2005): 5283–93. http://dx.doi.org/10.1091/mbc.e05-03-0210.
Full textAbstract:
The Wnt signaling pathway is important in the formation of neural crest cells in many vertebrates, but the downstream targets of neural crest induction by Wnt are largely unknown. Here, we examined quantitative changes in gene expression regulated by Wnt-mediated neural crest induction using quantitative PCR (QPCR). Induction was recapitulated in vitro by adding soluble Wnt to intermediate neural plate tissue cultured in collagen, and induced versus control tissue were assayed using gene-specific primers at times corresponding to premigratory (18 and 24 h) or early (36 h) stages of crest migration. The results show that Wnt signaling up-regulates in a distinct temporal pattern the expression of several genes normally expressed in the dorsal neural tube (slug, Pax3, Msx1, FoxD3, cadherin 6B) at “premigratory” stages. While slug is maintained in early migrating crest cells, Pax3, FoxD3, Msx1 and cadherin 6B all are down-regulated by the start of migration. These results differ from the temporal profile of these genes in response to the addition of recombinant BMP4, where gene expression seems to be maintained. Interestingly, expression of rhoB is unchanged or even decreased in response to Wnt-mediated induction at all times examined, though it is up-regulated by BMP signals. The temporal QPCR profiles in our culture paradigm approximate in vivo expression patterns of these genes before neural crest migration, and are consistent with Wnt being an initial neural crest inducer with additional signals like BMP and other factors maintaining expression of these genes in vivo. Our results are the first to quantitatively describe changes in gene expression in response to a Wnt or BMP signal during transformation of a neural tube cell into a migratory neural crest cell.
7
Hinck, L., WJ Nelson, and J. Papkoff. "Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin." Journal of Cell Biology 124, no. 5 (March 1, 1994): 729–41. http://dx.doi.org/10.1083/jcb.124.5.729.
Full textAbstract:
Wnt-1 homologs have been identified in invertebrates and vertebrates and play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (the Wnt-1 homolog) and armadillo participate in a signal transduction pathway important for cellular boundary formation in embryonic development, but functional interactions between the proteins are unknown. We have examined Wnt-1 function in mammalian cells in which armadillo (beta-catenin and plakoglobin) is known to bind to and regulate cadherin cell adhesion proteins. We show that Wnt-1 expression results in the accumulation of beta-catenin and plakoglobin. In addition, binding of beta-catenin to the cell adhesion protein, cadherin, is stabilized, resulting in a concomitant increase in the strength of calcium-dependent cell-cell adhesion. Thus, a consequence of the functional interaction between Wnt-1 and armadillo family members is the strengthening of cell-cell adhesion, which may lead to the specification of cellular boundaries.
8
Takebayashi-Suzuki, Kimiko, and Atsushi Suzuki. "Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation." Genes 11, no. 3 (March 24, 2020): 341. http://dx.doi.org/10.3390/genes11030341.
Full textAbstract:
During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal–ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior–posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos.
9
Wong, Siew Fen Lisa, Vikram Agarwal, Jennifer H. Mansfield, Nicolas Denans, Matthew G. Schwartz, Haydn M. Prosser, Olivier Pourquié, David P. Bartel, Clifford J. Tabin, and Edwina McGlinn. "Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs." Proceedings of the National Academy of Sciences 112, no. 35 (August 17, 2015): E4884—E4893. http://dx.doi.org/10.1073/pnas.1512655112.
Full textAbstract:
The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3′ UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae.
10
Swalla, Billie J., and Andrew B. Smith. "Deciphering deuterostome phylogeny: molecular, morphological and palaeontological perspectives." Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1496 (January 11, 2008): 1557–68. http://dx.doi.org/10.1098/rstb.2007.2246.
Full textAbstract:
Deuterostomes are a monophyletic group of animals that include the vertebrates, invertebrate chordates, ambulacrarians and xenoturbellids. Fossil representatives from most major deuterostome groups, including some phylum-level crown groups, are found in the Lower Cambrian, suggesting that evolutionary divergence occurred in the Late Precambrian, in agreement with some molecular clock estimates. Molecular phylogenies, larval morphology and the adult heart/kidney complex all support echinoderms and hemichordates as a sister grouping (Ambulacraria). Xenoturbellids are a relatively newly discovered phylum of worm-like deuterostomes that lacks a fossil record, but molecular evidence suggests that these animals are a sister group to the Ambulacraria. Within the chordates, cephalochordates share large stretches of chromosomal synteny with the vertebrates, have a complete Hox complex and are sister group to the vertebrates based on ribosomal and mitochondrial gene evidence. In contrast, tunicates have a highly derived adult body plan and are sister group to the vertebrates based on the analyses of concatenated genomic sequences. Cephalochordates and hemichordates share gill slits and an acellular cartilage, suggesting that the ancestral deuterostome also shared these features. Gene network data suggest that the deuterostome ancestor had an anterior–posterior body axis specified by Hox and Wnt genes, a dorsoventral axis specified by a BMP/chordin gradient, and was bilaterally symmetrical with left–right asymmetry determined by expression of nodal .
11
Leclère, Lucas, Tal S. Nir, Michael Bazarsky, Merav Braitbard, Dina Schneidman-Duhovny, and Uri Gat. "Dynamic Evolution of the Cthrc1 Genes, a Newly Defined Collagen-Like Family." Genome Biology and Evolution 12, no. 2 (February 1, 2020): 3957–70. http://dx.doi.org/10.1093/gbe/evaa020.
Full textAbstract:
Abstract Collagen triple helix repeat containing protein 1 (Cthrc1) is a secreted glycoprotein reported to regulate collagen deposition and to be linked to the Transforming growth factor β/Bone morphogenetic protein and the Wnt/planar cell polarity pathways. It was first identified as being induced upon injury to rat arteries and was found to be highly expressed in multiple human cancer types. Here, we explore the phylogenetic and evolutionary trends of this metazoan gene family, previously studied only in vertebrates. We identify Cthrc1 orthologs in two distant cnidarian species, the sea anemone Nematostella vectensis and the hydrozoan Clytia hemisphaerica, both of which harbor multiple copies of this gene. We find that Cthrc1 clade-specific diversification occurred multiple times in cnidarians as well as in most metazoan clades where we detected this gene. Many other groups, such as arthropods and nematodes, have entirely lost this gene family. Most vertebrates display a single highly conserved gene, and we show that the sequence evolutionary rate of Cthrc1 drastically decreased within the gnathostome lineage. Interestingly, this reduction coincided with the origin of its conserved upstream neighboring gene, Frizzled 6 (FZD6), which in mice has been shown to functionally interact with Cthrc1. Structural modeling methods further reveal that the yet uncharacterized C-terminal domain of Cthrc1 is similar in structure to the globular C1q superfamily domain, also found in the C-termini of collagens VIII and X. Thus, our studies show that the Cthrc1 genes are a collagen-like family with a variable short collagen triple helix domain and a highly conserved C-terminal domain structure resembling the C1q family.
12
Yang, Libo, Xiaoming Zhang, Chengzhang Liu, Jin Zhang, and Bo Dong. "MiR-92 Family Members Form a Cluster Required for Notochord Tubulogenesis in Urochordate Ciona savignyi." Genes 12, no. 3 (March 12, 2021): 406. http://dx.doi.org/10.3390/genes12030406.
Full textAbstract:
MicroRNAs are frequently clustered in the genome and polycistronically transcribed, regulating targeted genes in diverse signaling pathways. The miR-17-92 cluster is a typical miRNA cluster, playing crucial roles in the organogenesis and homeostasis of physiological processes in vertebrates. Here, we identified three miRNAs (csa-miR-92a, csa-miR-92b, and csa-miR-92c) that belonged to the miR-92 family and formed a miRNA cluster in the genome of a urochordate marine ascidian Ciona savignyi. Except for miR-92a and miR-92b, other homologs of the vertebrate miR-17-92 cluster members could not be identified in the Ciona genome. We further found that the mature sequences of urochordate miR-92 family members were highly conserved compared with the vertebrate species. The expression pattern revealed that three miR-92 family members had consistent expression levels in adult tissues and were predominantly expressed in heart and muscle tissue. We further showed that, at the embryonic and larval stages, csa-miR-92c was expressed in the notochord of embryos during 18–31 h post fertilization (hpf) by in situ hybridization. Knockout of csa-miR-92c resulted in the disorganization of notochord cells and the block of lumen coalescence in the notochord. Fibroblast growth factor (FGF), mitogen-activated protein kinase (MAPK), and wingless/integrated (Wnt)/planar cell polarity (PCP) signaling pathways might be involved in the regulatory processes, since a large number of core genes of these pathways were the predicted target genes of the miR-92 family. Taken together, we identified a miR-92 cluster in urochordate Ciona and revealed the expression patterns and the regulatory roles of its members in organogenesis. Our results provide expression and phylogenetic data on the understanding of the miR-92 miRNA cluster’s function during evolution.
13
Adusumilli, Lavanya, Nicola Facchinello, Cathleen Teh, Giorgia Busolin, Minh TN Le, Henry Yang, Giorgia Beffagna, et al. "miR-7 Controls the Dopaminergic/Oligodendroglial Fate through Wnt/β-catenin Signaling Regulation." Cells 9, no. 3 (March 13, 2020): 711. http://dx.doi.org/10.3390/cells9030711.
Full textAbstract:
During the development of the central nervous system, the proliferation of neural progenitors and differentiation of neurons and glia are tightly regulated by different transcription factors and signaling cascades, such as the Wnt and Shh pathways. This process takes place in cooperation with several microRNAs, some of which evolutionarily conserved in vertebrates, from teleosts to mammals. We focused our attention on miR-7, as its role in the regulation of cell signaling during neural development is still unclear. Specifically, we used human stem cell cultures and whole zebrafish embryos to study, in vitro and in vivo, the role of miR-7 in the development of dopaminergic (DA) neurons, a cell type primarily affected in Parkinson’s disease. We demonstrated that the zebrafish homologue of miR-7 (miR-7a) is expressed in the forebrain during the development of DA neurons. Moreover, we identified 143 target genes downregulated by miR-7, including the neural fate markers TCF4 and TCF12, as well as the Wnt pathway effector TCF7L2. We then demonstrated that miR-7 negatively regulates the proliferation of DA-progenitors by inhibiting Wnt/β-catenin signaling in zebrafish embryos. In parallel, miR-7 positively regulates Shh signaling, thus controlling the balance between oligodendroglial and DA neuronal cell fates. In summary, this study identifies a new molecular cross-talk between Wnt and Shh signaling pathways during the development of DA-neurons. Being mediated by a microRNA, this mechanism represents a promising target in cell differentiation therapies for Parkinson’s disease.
14
Bloomquist, Ryan F., Nicholas F. Parnell, Kristine A. Phillips, Teresa E. Fowler, Tian Y. Yu, Paul T. Sharpe, and J. Todd Streelman. "Coevolutionary patterning of teeth and taste buds." Proceedings of the National Academy of Sciences 112, no. 44 (October 19, 2015): E5954—E5962. http://dx.doi.org/10.1073/pnas.1514298112.
Full textAbstract:
Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium.
15
Tada, M., and J. C. Smith. "Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway." Development 127, no. 10 (May 15, 2000): 2227–38. http://dx.doi.org/10.1242/dev.127.10.2227.
Full textAbstract:
Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, we have screened for downstream target genes of Brachyury (Tada, M., Casey, E., Fairclough, L. and Smith, J. C. (1998) Development 125, 3997–4006). This approach has now allowed us to isolate Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-En(R). Overexpression of a dominant-negative form of Xwnt11, like overexpression of Xbra-En(R), inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signalling pathway and also by a truncated form of Dsh which cannot signal through the canonical Wnt pathway involving GSK-3 and (beta)-catenin. Together, our results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signalling in Drosophila.
16
Tan, Yinfei, and Joseph R. Testa. "DLX Genes: Roles in Development and Cancer." Cancers 13, no. 12 (June 15, 2021): 3005. http://dx.doi.org/10.3390/cancers13123005.
Full textAbstract:
Homeobox genes control body patterning and cell-fate decisions during development. The homeobox genes consist of many families, only some of which have been investigated regarding a possible role in tumorigenesis. Dysregulation of HOX family genes have been widely implicated in cancer etiology. DLX homeobox genes, which belong to the NK-like family, exert dual roles in development and cancer. The DLX genes are the key transcription factors involved in regulating the development of craniofacial structures in vertebrates. The three DLX bigenes have overlapping expression in the branchial arches. Disruption of DLX function has destructive consequences in organogenesis and is associated with certain congenital disorders in humans. The role of DLX genes in oncogenesis is only beginning to emerge. DLX2 diminishes cellular senescence by regulating p53 function, whereas DLX4 has been associated with metastasis in breast cancer. In human ovarian cancer cells, DLX5 is essential for regulating AKT signaling, thereby promoting cell proliferation and survival. We previously implicated Dlx5 as an oncogene in murine T-cell lymphoma driven by a constitutively active form of Akt2. In this mouse model, overexpression of Dlx5 was caused by a chromosomal rearrangement that juxtaposed the Tcr-beta promoter region near the Dlx5 locus. Moreover, transgenic mice overexpressing Dlx5, specifically in immature T-cells, develop spontaneous thymic lymphomas. Oncogenesis in this mouse model involves binding of Dlx5 to the Notch1 and Notch3 gene loci to activate their transcription. Dlx5 also cooperates with Akt signaling to accelerate lymphomagenesis by activating Wnt signaling. We also discuss the fact that human DLX5 is aberrantly expressed in several human malignancies.
17
Tian, Liang, Aiyou Wen, Shusheng Dong, and Peishi Yan. "Molecular Characterization of Microtubule Affinity-Regulating Kinase4 from Sus scrofa and Promotion of Lipogenesis in Primary Porcine Placental Trophoblasts." International Journal of Molecular Sciences 20, no. 5 (March 9, 2019): 1206. http://dx.doi.org/10.3390/ijms20051206.
Full textAbstract:
This study aimed to characterize the full-length cDNA of MARK4 in Sus scrofa, and evaluated its potential role in the regulation of lipid accumulation in pig placental trophoblasts and analyzed signaling pathways involved, thereby providing insights into mechanisms for placental lipotoxicity induced by excessive back-fat during pregnancy of sows. The cDNA obtained with 5′ and 3′ RACE amplification covered 3216 bp with an open reading frame of 2259 bp encoding 752 amino acids. Multiple alignments and phylogenetic analysis revealed MARK4 protein of Sus scrofa had a high homology (95%–99%) to that of other higher vertebrates. After transfection, enhanced MARK4 significantly promoted lipogenesis in pig trophoblasts, as evidenced by accelerated lipid accumulation and consistently increased mRNA expressions of lipogenic genes DGAT1, LPIN1, LPIN3, LPL, PPARδ and SREBP-1c. Meanwhile, PPARγ remarkably inhibited the stimulating effect of MARK4 on non-receptor-mediated lipid accumulation in trophoblasts. Further analyses revealed WNT signaling enhanced lipid accumulation and activation of MARK4 in pig trophoblast cells. Finally, we demonstrated that WNT/β-catenin signal pathway is involved in MARK4 activated lipogenesis. These results suggest that MARK4 promotes lipid accumulation in porcine placental trophoblasts and can be considered as a potential regulator of lipotoxicity associated with maternal obesity in the pig placenta.
18
Vizzini, Aiti, Angela Bonura, Laura La Paglia, Antonino Fiannaca, Massimo La Rosa, Alfonso Urso, and Vincenzo Arizza. "ceRNA Network Regulation of TGF-β, WNT, FOXO, Hedgehog Pathways in the Pharynx of Ciona robusta." International Journal of Molecular Sciences 22, no. 7 (March 28, 2021): 3497. http://dx.doi.org/10.3390/ijms22073497.
Full textAbstract:
The transforming growth factor-β (TGF-β) family of cytokines performs a multifunctional signaling, which is integrated and coordinated in a signaling network that involves other pathways, such as Wintless, Forkhead box-O (FOXO) and Hedgehog and regulates pivotal functions related to cell fate in all tissues. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from immune system homeostasis to the quiescence and self-renewal of hematopoietic stem cells (HSCs). Recently an important role in post-transcription regulation has been attributed to two type of ncRNAs: microRNAs and pseudogenes. Ciona robusta, due to its philogenetic position close to vertebrates, is an excellent model to investigate mechanisms of post-transcriptional regulation evolutionarily highly conserved in immune homeostasis. The combined use of NGS and bioinformatic analyses suggests that in the pharynx, the hematopoietic organ of Ciona robusta, the Tgf-β, Wnt, Hedgehog and FoxO pathways are involved in tissue homeostasis, as they are in human. Furthermore, ceRNA network interactions and 3′UTR elements analyses of Tgf-β, Wnt, Hedgehog and FoxO pathways genes suggest that different miRNAs conserved (cin-let-7d, cin-mir-92c, cin-mir-153), species-specific (cin-mir-4187, cin-mir-4011a, cin-mir-4056, cin-mir-4150, cin-mir-4189, cin-mir-4053, cin-mir-4016, cin-mir-4075), pseudogenes (ENSCING00000011392, ENSCING00000018651, ENSCING00000007698) and mRNA 3′UTR elements are involved in post-transcriptional regulation in an integrated way in C. robusta.
19
Ganis, Jared J., Elizabeth B. Riley, James Palis, and Leonard I. Zon. "A Screen for Regulators of Globin Switching in the Zebrafish Embryo." Blood 120, no. 21 (November 16, 2012): 826. http://dx.doi.org/10.1182/blood.v120.21.826.826.
Full textAbstract:
Abstract Abstract 826 The switching of the globin genes involves critical transcriptional regulators such as BCL11A, EKLF and SOX6, and the induction of fetal globin has been shown to ameliorate the symptoms of diseases such as sickle cell anemia. Recently, there has been interest in driving iPS cells to produce mature red cells that express adult globin genes in an attempt to make these cells therapeutically useful. Here, to understand hemoglobin switching and the molecular pathways that allow the establishment of an adult fate in embryonic tissues, we utilized a screening approach in the zebrafish model. The concept of the screen is to find transcription factors that are expressed in a stage-specific manner, and manipulate the expression of these genes to alter the cell fate of embryonic erythroid cells. In order to generate a candidate list of genes, microarray analysis was performed on murine yolk sac, fetal liver and adult derived red blood cells and red blood cell precursors, which express unique sets of globin genes. Pair-wise comparison of these populations yielded 879 unique differentially regulated genes. GO term analysis was used to narrow the list to 49 transcription factors. We focused on the transcription factors that might increase adult globin expression in the embryo based on their differential expression in the microarrays. Morpholinos were used to knock down these 24 genes by individually injecting each into one-cell stage embryos, allowing the embryos to reach 24 hpf and performing in situ hybridization for the adult globin gene αa1. The number of adult globin positive cells present in each embryo was counted for a clutch control group, which on average has 2–4 positive cells per embryo, and three doses of morpholino. We identified 4 genes, Tcf7l2, Ncoa1, Hif1al and E2F5, the knock down of which results in a significant increase in the number of adult globin positive cells in at least one dose of morpholino (control [n=53, mean=6.34], 6ng [n=56, mean=15.07], p=<0.0001; control [n=35, mean=1.543], 4ng [n=56, mean=2.75], p=<0.01; control [n=19, mean=1.368], 12ng [n=16, mean=6.188], p=<0.0001; control [n=44, mean=1.091], 4ng [n=30, mean=2.7], p=<0.05, respectively). Pair-wise knock down of these genes were also tested, and the combinations of Ncoa1 and E2F5, Tcf7l2 and E2F5 and Tcf7l2 and Ncoa1 were found to synergistically increase the number of adult globin expressing cells (control [n=49, mean=0.5306], knock down [n=38, mean=9.895], p=<0.0001; control [n=49, mean=7.633], knock down [n=54, mean=17.41], p=<0.0001; control [n=20, mean=2.95], knock down [n=28, mean=too numerous to count], p=<0.0001, respectively). The combined knock down of Tcf7l2 and Ncoa1 was both the strongest inducer of adult globin expression and had the lowest toxicity of the pair-wise combinations. Further characterization of this phenotype shows that, while many globin genes are up regulated, both of the adult globin genes, αa1 and βa1, are upregulated to a higher degree than other globin genes. In order to determine if the Wnt pathway is responsible for phenotype observed with the Tcf7l2 morpholino, we tested the Wnt pathway inhibitors IWR1 and XAV939. Both drugs phenocopied the Tcf7l2 knockdown response. In addition, XAV939 synergies with the Ncoa1 morpholino to enhance the increase in adult globin observed in a similar manner to Tcf7l2 knockdown. These results indicate that modulation of Wnt signaling, rather than a Wnt-independent function of Tcf7l2, is responsible for the phenotype and regulation of globin gene expression. Chip-Seq analysis of Ncoa1 occupancy in the erythroid cell line K562 was performed to examine potential mechanisms of action. Significant binding was observed at the enhancers of the α- and β-globin loci, indicating that the nuclear hormone receptor pathway may be acting directly on the globin loci to modulate globin expression patterns. These results indicate that Wnt signaling in combination with alterations of other pathways regulated by Ncoa1 are responsible for stage-specific globin expression. Our studies have impact on the understanding of globin switching in vertebrates, and could establish new methods to activate specific globins clinically, and to make iPS cells form adult-type tissues. Disclosures: Zon: Fate Therapeutics: Founder Other.
20
Parr, Brian A., and Andrew P. McMahon. "Wnt genes and vertebrate development." Current Opinion in Genetics & Development 4, no. 4 (August 1994): 523–28. http://dx.doi.org/10.1016/0959-437x(94)90067-d.
Full text
21
Prathibha, Yarikipati, and Balasubramanian Senthilkumaran. "Involvement of pax2 in ovarian development and recrudescence of catfish: a role in steroidogenesis." Journal of Endocrinology 231, no. 3 (December 2016): 181–95. http://dx.doi.org/10.1530/joe-16-0103.
Full textAbstract:
PAX2, a member of paired box family, is an essential transcription factor for the organ development in vertebrates including teleosts, yet no evidence has been shown for its involvement in reproduction. To study this, partial- and/or full-length cDNA of pax2 was isolated from the ovary of catfish, Clarias batrachus, along with its other Pax family members, pax1 and pax9. Tissue distribution and ontogeny expression analysis indicated the prevalence of pax2 but not pax1 and pax9 in ovary. Varied phase-wise expression during ovarian cycle and elevation of pax2 after human chorionic gonadotropin induction showed probable regulation by gonadotropins. Pax2 could be localized in various stages of oocytes and in follicular layer of vitellogenic and post-vitellogenic oocytes. To assess the functional significance of pax2, transient RNA silencing was performed using primary catfish ovarian follicle culture, in vitro, and in catfish, in vivo, through ovary-targeted injection of PEI-esiRNA. Pax2 siRNA treatment reduced the expression of various transcripts related to ovarian development like signaling molecules such as wnt4 and wnt5, estrogen receptors, several steroidogenic enzymes and transcription factors. These transitions in transcript levels might have been mediated by Pax2 acting upstream of wnt4/5 that may play a role in steroidogenesis and/or ovarian development along with ad4bp/sf-1 or by direct or indirect interaction with steroidogenic enzyme genes, which is evident from the change in the levels of serum estradiol-17β but not 17α,20β-dihydroxy-4-pregnen-3-one. Taken together, it seems that pax2 has a plausible role during ovarian development and/or recrudescence of catfish either directly or indirectly through Wnt signaling pathway.
22
Dickinson, Mary E., and Andrew P. McMahon. "The role of Wnt genes in vertebrate development." Current Opinion in Genetics & Development 2, no. 4 (January 1992): 562–66. http://dx.doi.org/10.1016/s0959-437x(05)80172-8.
Full text
23
MATTHEWS, J. B., O. LAZARI, A. J. DAVIDSON, S. WARREN, and M. E. SELKIRK. "A tryptophan amphiphilic tetramerization domain-containing acetylcholinesterase from the bovine lungworm, Dictyocaulus viviparus." Parasitology 133, no. 3 (May 24, 2006): 381–87. http://dx.doi.org/10.1017/s0031182006000345.
Full textAbstract:
Acetylcholine (ACh) is one of an array of neurotransmitters used by invertebrates and, analogous to vertebrate nervous systems, acetylcholinesterase (AChE) regulates synaptic levels of this transmitter. Similar to other invertebrates, nematodes possess several AChE genes. This is in contrast to vertebrates, which have a single AChE gene, transcripts of which are alternatively spliced to produce different types of the enzyme which vary at their C-termini. Parasitic nematodes have a repertoire of AChE genes which include those encoding neuromuscular AChEs and those genes which code for secreted AChEs. The latter proteins exist as soluble monomers released by the parasite during infection and these AChE are distinct from those enzymes which the nematodes use for synaptic transmission in their neuromuscular system. Thus far, Dictyocaulus viviparus is the only animal-parasitic nematode for which distinct genes that encode both neuromuscular and secreted AChEs have been defined. Here, we describe the isolation and characterization of a cDNA encoding a putative neuromuscular AChE from D. viviparus which contains a tryptophan amphiphilic tetramerization (WAT) domain at its C-terminus analogous to the common ‘tailed’ AChE form found in the neuromuscular systems of vertebrates and in the ACE-1 AChE from Caenorhabditis elegans. This enzyme differs from the previously isolated, D. viviparus neuromuscular AChE (Dv-ACE-2), which is a glycosylphosphatidylinositol-anchored variant analogous to vertebrate ‘hydrophobic’ AChE.
24
Krauss, S., V. Korzh, A. Fjose, and T. Johansen. "Expression of four zebrafish wnt-related genes during embryogenesis." Development 116, no. 1 (September 1, 1992): 249–59. http://dx.doi.org/10.1242/dev.116.1.249.
Full textAbstract:
The wnt gene family codes for a group of cysteine-rich, secreted proteins, which are differentially expressed in the developing embryo and are possibly involved in cellular communication. Here, we describe the polymerase chain reaction based cloning and embryonic expression patterns of four zebrafish wnt-related sequences; wnt[a], wnt[b], wnt[c] and wnt[d]. One of these genes, wnt[a], is a potential homologue of murine Wnt-3, while the other three genes most likely represent new members of the vertebrate wnt gene family. In zebrafish embryos, transcripts of wnt[a] are confined to the dorsal diencephalon, the dorsal midbrain, the rhombic lips and the dorsal portions of the spinal cord. wnt[b] is expressed in the tail bud and at considerably lower levels in the mesoderm of the head. wnt[c] transcripts are present within the diencephalon and the posterior midbrain whereas wnt[d] shows a surprisingly similar expression pattern to zebrafish wnt-1. By analogy to wnt-1, it is likely that the members of the zebrafish wnt gene family play an important role in cell-to-cell signalling during pattern formation in the neural tube and the tail bud.
25
Grove, E. A., S. Tole, J. Limon, L. Yip, and C. W. Ragsdale. "The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice." Development 125, no. 12 (June 15, 1998): 2315–25. http://dx.doi.org/10.1242/dev.125.12.2315.
Full textAbstract:
In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.
26
Sumanas, S., P. Strege, J. Heasman, and S. C. Ekker. "The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning." Development 127, no. 9 (May 1, 2000): 1981–90. http://dx.doi.org/10.1242/dev.127.9.1981.
Full textAbstract:
We have isolated one member of the frizzled family of wnt receptors from Xenopus (Xfz7) to study the role of cell-cell communication in the establishment of the vertebrate axis. We demonstrate that this maternally encoded protein specifically synergizes with wnt proteins in ectopic axis induction. Embryos derived from oocytes depleted of maternal Xfz7 RNA by antisense oligonucleotide injection are deficient in dorsoanterior structures. Xfz7-depleted embryos are deficient in dorsal but not ventral mesoderm due to the reduced expression of the wnt target genes siamois, Xnr3 and goosecoid. These signaling defects can be restored by the addition of beta-catenin but not Xwnt8b. Xfz7 thus functions upstream of the known GSK-3/axin/beta-catenin intracellular signaling complex in vertebrate dorsoventral mesoderm specification.
27
Westfall, Trudi A., Ryan Brimeyer, Jen Twedt, Jean Gladon, Andrea Olberding, Makoto Furutani-Seiki, and Diane C. Slusarski. "Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/β-catenin activity." Journal of Cell Biology 162, no. 5 (September 1, 2003): 889–98. http://dx.doi.org/10.1083/jcb.200303107.
Full textAbstract:
We provide genetic evidence defining a role for noncanonical Wnt function in vertebrate axis formation. In zebrafish, misexpression of Wnt-4, -5, and -11 stimulates calcium (Ca2+) release, defining the Wnt/Ca2+ class. We describe genetic interaction between two Wnt/Ca2+ members, Wnt-5 (pipetail) and Wnt-11 (silberblick), and a reduction of Ca2+ release in Wnt-5/pipetail. Embryos genetically depleted of both maternal and zygotic Wnt-5 product exhibit cell movement defects as well as hyperdorsalization and axis-duplication phenotypes. The dorsalized phenotypes result from increased β-catenin accumulation and activation of downstream genes. The Wnt-5 loss-of-function defect is consistent with Ca2+ modulation having an antagonistic interaction with Wnt/β-catenin signaling.
28
Eisenberg, Leonard M., and Carol A. Eisenberg. "Evaluating the Role of Wnt Signal Transduction in Promoting the Development of the Heart." Scientific World JOURNAL 7 (2007): 161–76. http://dx.doi.org/10.1100/tsw.2007.71.
Full textAbstract:
Wnts are a family of secreted signaling proteins that are encoded by 19 distinct genes in the vertebrate genome. These molecules initiate several signal transduction pathways: the canonical Wnt, Wnt/Ca2+, and Wnt/planar cell polarity pathways. Wnt proteins have major impact on embryonic development, tumor progression, and stem cell differentiation. Wnt signal transduction also influences the formation of the heart, yet many issues concerning the involvement of Wnt regulation in initiating cardiac development remain unresolved. In this review, we will examine the published record to discern (a) what has been shown by experimental studies on the participation of Wnt signaling in cardiogenesis, and (b) what are the important questions that need to be addressed to understand the importance and function of Wnt signal transduction in facilitating the development of the heart.
29
Lee, S. M., S. Tole, E. Grove, and A. P. McMahon. "A local Wnt-3a signal is required for development of the mammalian hippocampus." Development 127, no. 3 (February 1, 2000): 457–67. http://dx.doi.org/10.1242/dev.127.3.457.
Full textAbstract:
The mechanisms that regulate patterning and growth of the developing cerebral cortex remain unclear. Suggesting a role for Wnt signaling in these processes, multiple Wnt genes are expressed in selective patterns in the embryonic cortex. We have examined the role of Wnt-3a signaling at the caudomedial margin of the developing cerebral cortex, the site of hippocampal development. We show that Wnt-3a acts locally to regulate the expansion of the caudomedial cortex, from which the hippocampus develops. In mice lacking Wnt-3a, caudomedial cortical progenitor cells appear to be specified normally, but then underproliferate. By mid-gestation, the hippocampus is missing or represented by tiny populations of residual hippocampal cells. Thus, Wnt-3a signaling is crucial for the normal growth of the hippocampus. We suggest that the coordination of growth with patterning may be a general role for Wnts during vertebrate development.
30
Levay-Young, B. K., and M. Navre. "Growth and developmental regulation of wnt-2 (irp) gene in mesenchymal cells of fetal lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 262, no. 6 (June 1, 1992): L672—L683. http://dx.doi.org/10.1152/ajplung.1992.262.6.l672.
Full textAbstract:
The wnt gene family encodes a group of proteins implicated as intercellular signaling molecules in vertebrate development. Because many wnt genes are also expressed in the lung, we have examined whether the wnt family member wnt-2 (irp) plays a role in lung development. We have cloned rat wnt-2 and found that this cDNA detects multiple mRNAs expressed at high levels in fetal rat lung. Much lower levels were found in adult rat lung and other tissues, including, surprisingly, the mammary gland. The wnt-2 mRNA was also detected in human fetal lung fibroblast cell lines, where the mRNA levels were dramatically regulated by growth state as well as growth factor stimulation. In situ hybridization showed that, in fetal rat lung, wnt-2 mRNA expression is restricted to the mesenchyme; levels in the developing epithelium were indistinguishable from background. Based on the known properties of other wnt proteins, our data lead us to propose that wnt-2 may play a role in lung development by mediating intercellular interaction(s) between mesenchyme and epithelium.
31
Ye, Zhi, and David Kimelman. "Hox13 genes are required for mesoderm formation and axis elongation during early zebrafish development." Development 147, no. 22 (November 5, 2020): dev185298. http://dx.doi.org/10.1242/dev.185298.
Full textAbstract:
ABSTRACTThe early vertebrate embryo extends from anterior to posterior due to the addition of neural and mesodermal cells from a neuromesodermal progenitor (NMp) population located at the most posterior end of the embryo. In order to produce mesoderm throughout this time, the NMps produce their own niche, which is high in Wnt and low in retinoic acid. Using a loss-of-function approach, we demonstrate here that the two most abundant Hox13 genes in zebrafish have a novel role in providing robustness to the NMp niche by working in concert with the niche-establishing factor Brachyury to allow mesoderm formation. Mutants lacking both hoxa13b and hoxd13a in combination with reduced Brachyury activity have synergistic posterior body defects, in the strongest case producing embryos with severe mesodermal defects that phenocopy brachyury null mutants. Our results provide a new way of understanding the essential role of the Hox13 genes in early vertebrate development.This article has an associated ‘The people behind the papers’ interview.
32
Azambuja, Ana Paula, and Marcos Simoes-Costa. "A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest formation." PLOS Genetics 17, no. 1 (January 19, 2021): e1009296. http://dx.doi.org/10.1371/journal.pgen.1009296.
Full textAbstract:
The process of cell fate commitment involves sequential changes in the gene expression profiles of embryonic progenitors. This is exemplified in the development of the neural crest, a migratory stem cell population derived from the ectoderm of vertebrate embryos. During neural crest formation, cells transition through distinct transcriptional states in a stepwise manner. The mechanisms underpinning these shifts in cell identity are still poorly understood. Here we employ enhancer analysis to identify a genetic sub-circuit that controls developmental transitions in the nascent neural crest. This sub-circuit links Wnt target genes in an incoherent feedforward loop that controls the sequential activation of genes in the neural crest lineage. By examining the cis-regulatory apparatus of Wnt effector gene AXUD1, we found that multipotency factor SP5 directly promotes neural plate border identity, while inhibiting premature expression of specification genes. Our results highlight the importance of repressive interactions in the neural crest gene regulatory network and illustrate how genes activated by the same upstream signal become temporally segregated during progressive fate restriction.
33
Millen, K. J., C. C. Hui, and A. L. Joyner. "A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum." Development 121, no. 12 (December 1, 1995): 3935–45. http://dx.doi.org/10.1242/dev.121.12.3935.
Full textAbstract:
To gain insight into the molecular genetic basis of cerebellar patterning, the expression patterns of many vertebrate homologues of Drosophila segment polarity genes were examined during normal and abnormal cerebellar development, including members of the En, Wnt, Pax, Gli and Dvl gene families. Five of these genes were found to show transient, spatially restricted patterns of expression. Strikingly, expression of En-2, En-1, Wnt-7B and Pax-2 defined eleven similar sagittal domains at 17.5 dpc, reminiscent of the transient sagittal domains of expression of Purkinje cell markers which have been implicated in cerebellar afferent patterning. Postnatally, transient anterior/posterior differences in expression were observed for En-2, En-1, Gli and Wnt-7B dividing the cerebellum into anterior and posterior regions. The expression patterns of these genes were altered in cerebella of En-2 homozygous mutant mice, which show a cerebellar foliation patterning defect. Strikingly, four of the Wnt-7B expression domains that are adjacent to the En-2 domains are lost in En-2 mutant embryonic cerebella. These studies provide the first evidence of a potential network of regulatory genes that establish spatial cues in the developing cerebellum by dividing it into a grid of positional information required for patterning foliation and afferents. Taken together with previous gene expression studies, our data suggests that eleven sagittal domains and at least two anterior/posterior compartments are the basic elements of spatial information in the cerebellum.
34
Nishiyama, Masaaki, Keiko Nakayama, Ryosuke Tsunematsu, Tadasuke Tsukiyama, Akira Kikuchi, and Keiichi I. Nakayama. "Early Embryonic Death in Mice Lacking the β-Catenin-Binding Protein Duplin." Molecular and Cellular Biology 24, no. 19 (October 1, 2004): 8386–94. http://dx.doi.org/10.1128/mcb.24.19.8386-8394.2004.
Full textAbstract:
ABSTRACT The Wnt signaling pathway plays a pivotal role in vertebrate early development and morphogenesis. Duplin (axis duplication inhibitor) interacts with β-catenin and prevents its binding to Tcf, thereby inhibiting downstream Wnt signaling. Here we show that Duplin is expressed predominantly from early- to mid-stage mouse embryogenesis, and we describe the generation of mice deficient in Duplin. Duplin −/− embryos manifest growth retardation from embryonic day 5.5 (E5.5) and developmental arrest accompanied by massive apoptosis at E7.5. The mutant embryos develop into an egg cylinder but do not form a primitive streak or mesoderm. Expression of β-catenin target genes, including those for T (brachyury), Axin2, and cyclin D1, was not increased in Duplin −/− embryos, suggesting that the developmental defect is not simply attributable to upregulation of Wnt signaling caused by the lack of this inhibitor. These results suggest that Duplin plays an indispensable role, likely by a mechanism independent of inhibition of Wnt signaling, in mouse embryonic growth and differentiation at an early developmental stage.
35
Shahjahan, Md. "Skeletal muscle development in vertebrate animals." Asian Journal of Medical and Biological Research 1, no. 2 (November 23, 2015): 139–48. http://dx.doi.org/10.3329/ajmbr.v1i2.25592.
Full textAbstract:
This review covers the pre- and post-natal development of skeletal muscle of vertebrate animals with cellular and molecular levels. The formation of skeletal muscle initiates from paraxial mesoderm during embryogenesis of individuals which develops somites and subsequently forms dermomyotome derived myotome to give rise axial musculature. This process (myogenesis) includes stem and progenitor cell maintenance, lineage specification, and terminal differentiation to form myofibrils consequent muscle fibers which control muscle mass and its multiplication. The main factors of muscle growth are proliferation and differentiation of myogenic cells in prenatal stage and also the growth of satellite cells at postnatal stage. There is no net increase in the number of muscle fibers in vertebrate animals after hatch or birth except fish. The development of muscle is characterized by hyperplasia and hypertrophy in prenatal and postnatal stages of individuals, respectively, through Wnt signalling pathway including environment, nutrition, sex, feed, growth and myogenic regulatory factors. Therefore further studies could elucidate new growth related genes, markers and factors to enhance meat production and enrich knowledge on muscle growth.Asian J. Med. Biol. Res. June 2015, 1(2): 139-148
36
Garriock, Robert J., Andrew S. Warkman, Stryder M. Meadows, Susan D'Agostino, and Paul A. Krieg. "Census of vertebrate Wnt genes: Isolation and developmental expression ofXenopus Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16." Developmental Dynamics 236, no. 5 (2007): 1249–58. http://dx.doi.org/10.1002/dvdy.21156.
Full text
37
Wang, Hong-yan, Yan-xin Huang, Li-hua Zheng, Yong-li Bao, Lu-guo Sun, Yin Wu, Chun-lei Yu, et al. "Modelling Coupled Oscillations in the Notch, Wnt, and FGF Signaling Pathways during Somitogenesis: A Comprehensive Mathematical Model." Computational Intelligence and Neuroscience 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/387409.
Full textAbstract:
Somite formation in the early stage of vertebrate embryonic development is controlled by a complicated gene network named segmentation clock, which is defined by the periodic expression of genes related to the Notch, Wnt, and the fibroblast growth factor (FGF) pathways. Although in recent years some findings about crosstalk among the Notch, Wnt, and FGF pathways in somitogenesis have been reported, the investigation of their crosstalk mechanisms from a systematic point of view is still lacking. In this study, a more comprehensive mathematical model was proposed to simulate the dynamics of the Notch, Wnt, and FGF pathways in the segmentation clock. Simulations and bifurcation analyses of this model suggested that the concentration gradients of both Wnt, and FGF signals along the presomitic mesoderm (PSM) are corresponding to the whole process from start to stop of the segmentation clock. A number of highly sensitive parameters to the segmentation clock’s oscillatory pattern were identified. By further bifurcation analyses for these sensitive parameters, and several complementary mechanisms in respect of the maintenance of the stable oscillation of the segmentation clock were revealed.
38
Caraballo, Diego A., Lucila I. Buzzi, Carlos P. Modenutti, Ana Acosta-Montalvo, Olga A. Castro, and María S. Rossi. "Origin and Evolution of Two Independently Duplicated Genes Encoding UDP- Glucose: Glycoprotein Glucosyltransferases in Caenorhabditis and Vertebrates." G3: Genes|Genomes|Genetics 10, no. 2 (December 3, 2019): 755–68. http://dx.doi.org/10.1534/g3.119.400868.
Full textAbstract:
UDP- glucose: glycoprotein glucosyltransferase (UGGT) is a protein that operates as the gatekeeper for the endoplasmic reticulum (ER) quality control mechanism of glycoprotein folding. It is known that vertebrates and Caenorhabditis genomes harbor two uggt gene copies that exhibit differences in their properties.Bayesian phylogenetic inference based on 195 UGGT and UGGT-like protein sequences of an ample spectrum of eukaryotic species showed that uggt genes went through independent duplications in Caenorhabditis and vertebrates. In both lineages, the catalytic domain of the duplicated genes was subjected to a strong purifying selective pressure, while the recognition domain was subjected to episodic positive diversifying selection. Selective relaxation in the recognition domain was more pronounced in Caenorhabditis uggt-b than in vertebrates uggt-2. Structural bioinformatics analysis revealed that Caenorhabditis UGGT-b protein lacks essential sequences proposed to be involved in the recognition of unfolded proteins. When we assayed glucosyltrasferase activity of a chimeric protein composed by Caenorhabditis uggt-b recognition domain fused to S. pombe catalytic domain expressed in yeast, no activity was detected.The present results support the conservation of the UGGT activity in the catalytic domain and a putative divergent function of the recognition domain for the UGGT2 protein in vertebrates, which would have gone through a specialization process. In Caenorhabditis, uggt-b evolved under different constraints compared to uggt-a which, by means of a putative neofunctionalization process, resulted in a non-redundant paralog. The non-canonical function of uggt-b in the worm lineage highlights the need to take precautions before generalizing gene functions in model organisms.
39
Itoh, Motoyuki, Tetsuhiro Kudoh, Michael Dedekian, Cheol-Hee Kim, and Ajay B. Chitnis. "A role foriro1andiro7in the establishment of an anteroposterior compartment of the ectoderm adjacent to the midbrain-hindbrain boundary." Development 129, no. 10 (May 15, 2002): 2317–27. http://dx.doi.org/10.1242/dev.129.10.2317.
Full textAbstract:
We have identified a novel Iroquois (Iro) gene, iro7, in zebrafish. iro7 is expressed during gastrulation along with iro1 in a compartment of the dorsal ectoderm that includes the prospective midbrain-hindbrain domain, the adjacent neural crest and the trigeminal placodes in the epidermis. The iro1 and iro7 expression domain is expanded in headless and masterblind mutants, which are characterized by exaggerated Wnt signaling. Early expansion of iro1 and iro7 expression in these mutants correlates with expansion of the midbrain-hindbrain boundary (MHB) domain, the neural crest and trigeminal neurons, raising the possibility that iro1 and iro7 have a role in determination of these ectodermal derivatives. A knockdown of iro7 function revealed that iro7 is essential for the determination of neurons in the trigeminal placode. In addition, a knockdown of both iro1 and iro7 genes uncovered their essential roles in neural crest development and establishment of the isthmic organizer at the MHB. These results suggest a new role for Iro genes in establishment of an ectodermal compartment after Wnt signaling in vertebrate development. Furthermore, analysis of activator or repressor forms of iro7 suggests that iro1 and iro7 are likely to function as repressors in establishment of the isthmic organizer and neural crest, and Iro genes may have dual functions as repressors and activators in neurogenesis.
40
Peifer, Mark, Sandra Orsulic, Li-Mei Pai, and Joseph Loureiro. "A model system for cell adhesion and signal transduction in Drosophila." Development 119, Supplement (December 1, 1993): 163–76. http://dx.doi.org/10.1242/dev.119.supplement.163.
Full textAbstract:
Cells must cooperate and communicate to form a multicellular animal. Information about the molecules required for these processes have come from a variety of sources; the convergence between the studies of particular molecules by vertebrate cell biologists and the genes identified by scientists investigating development in Drosophila has been especially fruitful. We are interested in the connection between cadherin proteins that regulate cell-cell adhesion and the wingless/wnt-1 cell-cell signaling molecules controlling pattern formation during development. The Drosophila segment polarity gene armadillo, homolog of the vertebrate adherens junction protein-catenin, is required for both cell adhesion and wg signaling. We review what is known about wingless signaling in Drosophila, and discuss the role of cell-cell junctions in both cell adhesion and cell communication. We then describe the results of our preliminary structure-function analysis of Armadillo protein in both cell adhesion and wingless signaling. Finally, we discuss evidence supporting a direct role for Armadillo and adherens junction in transduction of wingless signal.
41
Ding, Yi, Diego Ploper, Eric A. Sosa, Gabriele Colozza, Yuki Moriyama, Maria D. J. Benitez, Kelvin Zhang, Daria Merkurjev, and Edward M. De Robertis. "Spemann organizer transcriptome induction by early beta-catenin, Wnt, Nodal, and Siamois signals in Xenopus laevis." Proceedings of the National Academy of Sciences 114, no. 15 (March 27, 2017): E3081—E3090. http://dx.doi.org/10.1073/pnas.1700766114.
Full textAbstract:
The earliest event in Xenopus development is the dorsal accumulation of nuclear β-catenin under the influence of cytoplasmic determinants displaced by fertilization. In this study, a genome-wide approach was used to examine transcription of the 43,673 genes annotated in the Xenopus laevis genome under a variety of conditions that inhibit or promote formation of the Spemann organizer signaling center. Loss of function of β-catenin with antisense morpholinos reproducibly reduced the expression of 247 mRNAs at gastrula stage. Interestingly, only 123 β-catenin targets were enriched on the dorsal side and defined an early dorsal β-catenin gene signature. These genes included several previously unrecognized Spemann organizer components. Surprisingly, only 3 of these 123 genes overlapped with the late Wnt signature recently defined by two other groups using inhibition by Dkk1 mRNA or Wnt8 morpholinos, which indicates that the effects of β-catenin/Wnt signaling in early development are exquisitely regulated by stage-dependent mechanisms. We analyzed transcriptome responses to a number of treatments in a total of 46 RNA-seq libraries. These treatments included, in addition to β-catenin depletion, regenerating dorsal and ventral half-embryos, lithium chloride treatment, and the overexpression of Wnt8, Siamois, and Cerberus mRNAs. Only some of the early dorsal β-catenin signature genes were activated at blastula whereas others required the induction of endomesoderm, as indicated by their inhibition by Cerberus overexpression. These comprehensive data provide a rich resource for analyzing how the dorsal and ventral regions of the embryo communicate with each other in a self-organizing vertebrate model embryo.
42
Ding, Yi, Gabriele Colozza, Eric A. Sosa, Yuki Moriyama, Samantha Rundle, Lukasz Salwinski, and Edward M. De Robertis. "Bighead is a Wnt antagonist secreted by the Xenopus Spemann organizer that promotes Lrp6 endocytosis." Proceedings of the National Academy of Sciences 115, no. 39 (September 12, 2018): E9135—E9144. http://dx.doi.org/10.1073/pnas.1812117115.
Full textAbstract:
The Xenopus laevis embryo has been subjected to almost saturating screens for molecules specifically expressed in dorsal Spemann organizer tissue. In this study, we performed high-throughput RNA sequencing of ectodermal explants, called animal caps, which normally give rise to epidermis. We analyzed dissociated animal cap cells that, through sustained activation of MAPK, differentiate into neural tissue. We also microinjected mRNAs for Cerberus, Chordin, FGF8, BMP4, Wnt8, and Xnr2, which induce neural or other germ layer differentiations. The searchable database provided here represents a valuable resource for the early vertebrate cell differentiation. These analyses resulted in the identification of a gene present in frog and fish, which we call Bighead. Surprisingly, at gastrula, it was expressed in the Spemann organizer and endoderm, rather than in ectoderm as we expected. Despite the plethora of genes already mined from Spemann organizer tissue, Bighead encodes a secreted protein that proved to be a potent inhibitor of Wnt signaling in a number of embryological and cultured cell signaling assays. Overexpression of Bighead resulted in large head structures very similar to those of the well-known Wnt antagonists Dkk1 and Frzb-1. Knockdown of Bighead with specific antisense morpholinos resulted in embryos with reduced head structures, due to increased Wnt signaling. Bighead protein bound specifically to the Wnt coreceptor lipoprotein receptor-related protein 6 (Lrp6), leading to its removal from the cell surface. Bighead joins two other Wnt antagonists, Dkk1 and Angptl4, which function as Lrp6 endocytosis regulators. These results suggest that endocytosis plays a crucial role in Wnt signaling.
43
Sykes, T. G., A. R. Rodaway, M. E. Walmsley, and R. K. Patient. "Suppression of GATA factor activity causes axis duplication in Xenopus." Development 125, no. 23 (December 1, 1998): 4595–605. http://dx.doi.org/10.1242/dev.125.23.4595.
Full textAbstract:
In Xenopus, the dorsoventral axis is patterned by the interplay between active signalling in ventral territories, and secreted antagonists from Spemann's organiser. Two signals are important in ventral cells, bone morphogenetic protein-4 (BMP-4) and Wnt-8. BMP-4 plays a conserved role in patterning the vertebrate dorsoventral axis, whilst the precise role of Wnt-8 and its relationship with BMP-4, are still unclear. Here we have investigated the role played by the GATA family of transcription factors, which are expressed in ventral mesendoderm during gastrulation and are required for the differentiation of blood and endodermal tissues. Injection ventrally of a dominant-interfering GATA factor (called G2en) induced the formation of secondary axes that phenocopy those induced by the dominant-negative BMP receptor. However, unlike inhibiting BMP signalling, inhibiting GATA activity in the ectoderm does not lead to neuralisation. In addition, analysis of gene expression in G2en injected embryos reveals that at least one known target gene for BMP-4, the homeobox gene Vent-2, is unaffected. In contrast, the expression of Wnt-8 and the homeobox gene Vent-1 is suppressed by G2en, whilst the organiser-secreted BMP antagonist chordin becomes ectopically expressed. These data therefore suggest that GATA activity is essential for ventral cell fate and that subsets of ventralising and dorsalising genes require GATA activity for their expression and suppression, respectively. Finally, using G2en, we show that suppression of Wnt-8 expression, in conjunction with blocked BMP signalling, does not lead to head formation, suggesting that the head-suppressing Wnt signal may not be Wnt-8.
44
Cox, R. T., L. M. Pai, J. R. Miller, S. Orsulic, J. Stein, C. A. McCormick, Y. Audeh, W. Wang, R. T. Moon, and M. Peifer. "Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal on its own." Development 126, no. 6 (March 15, 1999): 1327–35. http://dx.doi.org/10.1242/dev.126.6.1327.
Full textAbstract:
Drosophila Armadillo and its vertebrate homolog beta-catenin are key effectors of Wingless/Wnt signaling. In the current model, Wingless/Wnt signal stabilizes Armadillo/beta-catenin, which then accumulates in nuclei and binds TCF/LEF family proteins, forming bipartite transcription factors which activate transcription of Wingless/Wnt responsive genes. This model was recently challenged. Overexpression in Xenopus of membrane-tethered beta-catenin or its paralog plakoglobin activates Wnt signaling, suggesting that nuclear localization of Armadillo/beta-catenin is not essential for signaling. Tethered plakoglobin or beta-catenin might signal on their own or might act indirectly by elevating levels of endogenous beta-catenin. We tested these hypotheses in Drosophila by removing endogenous Armadillo. We generated a series of mutant Armadillo proteins with altered intracellular localizations, and expressed these in wild-type and armadillo mutant backgrounds. We found that membrane-tethered Armadillo cannot signal on its own; however it can function in adherens junctions. We also created mutant forms of Armadillo carrying heterologous nuclear localization or nuclear export signals. Although these signals alter the subcellular localization of Arm when overexpressed in Xenopus, in Drosophila they have little effect on localization and only subtle effects on signaling. This supports a model in which Armadillo's nuclear localization is key for signaling, but in which Armadillo intracellular localization is controlled by the availability and affinity of its binding partners.
45
Peifer, M., D. Sweeton, M. Casey, and E. Wieschaus. "wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo." Development 120, no. 2 (February 1, 1994): 369–80. http://dx.doi.org/10.1242/dev.120.2.369.
Full textAbstract:
wingless/wnt-1 signaling directs cell fate during development. Genetic analysis in Drosophila identified genes that may encode components of the wingless signal transduction system. Drosophila Armadillo, homolog of vertebrate beta-catenin, is required for wingless signaling. Unlike armadillo RNA, Armadillo protein accumulates non-uniformly in different cells of each embryonic segment. We found that cells alter their intracellular distribution of Armadillo in response to Wingless signal, accumulating increased levels of cytoplasmic Armadillo relative to those of membrane-associated protein. Levels of cytoplasmic Armadillo are also regulated by Zeste-White 3 kinase. Analysis of double mutants demonstrates that Armadillo's role in wingless signaling is direct, and that Armadillo functions downstream of both wingless and zeste-white 3. We present a model for the role of Armadillo stripes in transduction of wingless signal.
46
Clements, Wilson K., Karen G. Ong, Albert D. Kim, and David Traver. "Wnt16 Is Required for Specification of Vertebrate Hematopoietic Stem Cells through Notch." Blood 116, no. 21 (November 19, 2010): 2616. http://dx.doi.org/10.1182/blood.v116.21.2616.2616.
Full textAbstract:
Abstract Abstract 2616 Hematopoietic stem cells (HSCs) are self-renewing progenitor cells that provide all adult blood lineages over the lifetime of an individual. Understanding the signaling events that regulate specification of these cells during embryonic development is a key precondition to recapitulating those processes in vitro for the purposes of regenerative medicine. Here we report that non-canonical Wnt signaling by the conserved vertebrate ligand, Wnt16 is required for specification of HSCs in zebrafish. WNT16 was originally identified as a gene aberrantly expressed in pre-B acute lymphoblastic leukemia (ALL) cells containing the t(1;19) chromosomal translocation, leading to expression of E2A-PBX1. Wnt16 is expressed in mammals at times when hemogenic endothelial cells first appear in the dorsal aorta. In zebrafish, wnt16 is expressed in somites, which lie adjacent to the dorsal aorta. Knock down of Wnt16 function by injection of antisense morpholino oligonucleotides leads to loss of HSCs and definitive blood lineages, such as T-cells, during development. Non-blood tissues including vasculature appear largely unaffected. Thus, wnt16 is required for HSC specification. To better understand the Wnt16 signal transduction pathway, we examined its ability to activate transcription of target genes through β-catenin/Tcf-dependent “canonical” signaling. Although Wnt16 overexpression causes morphological abnormality, it does not yield ectopic expression of endogenous or transgenic canonical reporter genes at time points relevant to blood specification. Thus, Wnt16 signals independently of β-catenin/Tcf through a “non-canonical” Wnt pathway. Notch signaling is required for specification of HSCs across phyla. To determine whether Notch signaling is disrupted in Wnt16 morphants, we examined the expression of all Notch ligands and receptors in these animals and found that expression of two ligands, deltaC (dlc) and deltaD (dld) are decreased. Zebrafish mutants, homozygous for a null allele of dlc, and embryos injected with a dld morpholino each display decreased numbers of HSCs during development, but recover. Dlc mutants injected with dld morpholino show complete loss of HSCs. To determine whether defects in Notch signaling are responsible for loss of HSCs in Wnt16 morphants, we performed a rescue experiment. Transgenic animals carrying an inducible dominant activator of Notch target genes were injected with Wnt16 morpholino, and Notch activity was either induced or not. Wnt16 morphants with enforced Notch activity recovered HSC marker expression. Taken together, our results indicate that Wnt16 regulates expression of the Notch ligands dlc and dld, and these are redundantly required for HSC specification during development. Chimera experiments in mouse using wild type and Notch1-deficient cells indicate that there is a cell-autonomous requirement for Notch signaling in specification of HSCs. To determine when the first Notch-responsive cells that contribute to the adult hematopoietic system appear, we used animals carrying a transgene encoding a photconvertible, green-to-red Kaede protein under the control of a Notch-responsive promoter. By photoconverting all embryonic cells at various times during development, we determined that cells destined to become HSCs first experience a Notch signal at approximately the time when HSCs first appear, just before 24 hours post fertilization (hpf). At earlier time points, Notch responsive cells were present, but did not contribute to blood, although they did contribute to tissues in or near the dorsal aorta, which contains the hemogenic endothelium that gives rise to HSCs. Surprisingly, HSC rescue in Wnt16 morphants by Notch activation could only be achieved earlier than 16 hpf, long before a cell-autonomous Notch signal is received in pre-HSCs. Moreover, loss of the critical ligands, dlc and dld, in Wnt16 morphant animals was confined to somitic tissue prior to 20 hpf, while ligand expression in or near the dorsal aorta at later times was relatively normal. Together, our results strongly suggest a previously unappreciated, non-cell-autonomous requirement for Notch signaling in the somites. We hypothesize that somitic Notch signaling regulates a morphological process or expression of a relay signal required for HSC specification during development. Disclosures: No relevant conflicts of interest to declare.
47
Deardorff, Matthew A., Change Tan, Jean-Pierre Saint-Jeannet, and Peter S. Klein. "A role for frizzled 3 in neural crest development." Development 128, no. 19 (October 1, 2001): 3655–63. http://dx.doi.org/10.1242/dev.128.19.3655.
Full textAbstract:
Wnts are a large family of secreted molecules implicated in numerous developmental processes. Frizzled proteins are likely receptors for Wnts and are required for Wnt signaling in invertebrates. A large number of vertebrate frizzled genes have also been identified, but their roles in mediating specific responses to endogenous Wnts have not been well defined. Using a functional assay in Xenopus, we have performed a large screen to identify potential interactions between Wnts and frizzleds. We find that signaling by Xwnt1, but not other Wnts, can be specifically enhanced by frizzled 3 (Xfz3). As both Xfz3 and Xwnt1 are highly localized to dorsal neural tissues that give rise to neural crest, we examined whether Xfz3 mediates Xwnt1 signaling in the formation of neural crest. Xfz3 specifically induces neural crest in ectodermal explants and in embryos, similar to Xwnt1, and at lower levels of expression, synergizes with Xwnt1 in neural crest induction. Furthermore, loss of Xfz3 function, either by depletion with a Xfz3-directed morpholino antisense oligonucleotide or by expression of an inhibitory form of Xfz3 (Nfz3), prevents Xwnt1-dependent neural crest induction in ectodermal explants and blocks neural crest formation in whole embryos. These results show that Xfz3 is required for Xwnt1 signaling in the formation of the neural crest in the developing vertebrate embryo.
48
Shibata, Yuki, Yuta Tanizaki, Hongen Zhang, Hangnoh Lee, Mary Dasso, and Yun-Bo Shi. "Thyroid Hormone Receptor Is Essential for Larval Epithelial Apoptosis and Adult Epithelial Stem Cell Development but Not Adult Intestinal Morphogenesis during Xenopus tropicalis Metamorphosis." Cells 10, no. 3 (March 3, 2021): 536. http://dx.doi.org/10.3390/cells10030536.
Full textAbstract:
Vertebrate postembryonic development is regulated by thyroid hormone (T3). Of particular interest is anuran metamorphosis, which offers several unique advantages for studying the role of T3 and its two nuclear receptor genes, TRα and TRβ, during postembryonic development. We have recently generated TR double knockout (TRDKO) Xenopus tropicalis animals and reported that TR is essential for the completion of metamorphosis. Furthermore, TRDKO tadpoles are stalled at the climax of metamorphosis before eventual death. Here we show that TRDKO intestine lacked larval epithelial cell death and adult stem cell formation/proliferation during natural metamorphosis. Interestingly, TRDKO tadpole intestine had premature formation of adult-like epithelial folds and muscle development. In addition, T3 treatment of premetamorphic TRDKO tadpoles failed to induce any metamorphic changes in the intestine. Furthermore, RNA-seq analysis revealed that TRDKO altered the expression of many genes in biological pathways such as Wnt signaling and the cell cycle that likely underlay the inhibition of larval epithelial cell death and adult stem cell development caused by removing both TR genes. Our data suggest that liganded TR is required for larval epithelial cell degeneration and adult stem cell formation, whereas unliganded TR prevents precocious adult tissue morphogenesis such as smooth-muscle development and epithelial folding.
49
Yang, Xiao-Dong, Tejas R. Karhadkar, Jessica Medina, Scott M. Robertson, and Rueyling Lin. "β-Catenin–related protein WRM-1 is a multifunctional regulatory subunit of the LIT-1 MAPK complex." Proceedings of the National Academy of Sciences 112, no. 2 (December 29, 2014): E137—E146. http://dx.doi.org/10.1073/pnas.1416339112.
Full textAbstract:
Vertebrate β-catenin has two functions, as a structural component of the adherens junction in cell adhesion and as the T-cell factor (TCF) transcriptional coactivator in canonical Wnt (wingless-related integration site) signaling. These two functions are split between three of the four β-catenin–related proteins present in the round worm Caenorhabditis elegans. The fourth β-catenin–related protein, WRM-1, exhibits neither of these functions. Instead, WRM-1 binds the MAPK loss of intestine 1 (LIT-1), and these two proteins have been shown to be essential for the transcription of Wnt target genes by phosphorylating and regulating the nuclear level of the sole worm TCF protein. We showed previously that WRM-1 binds to worm TCF and functions as the substrate-binding subunit for LIT-1. In this study, we show that phosphorylation of T220 in the activation loop is essential for LIT-1 kinase activity in vivo and in vitro. T220 can be phosphorylated either through LIT-1 autophosphorylation or directly by the upstream MAP3K MOM-4. Our data support a model in which WRM-1, which can undergo homotypic interaction, binds LIT-1 and thereby generates a kinase complex in which LIT-1 molecules are situated in a conformation enabling autophosphorylation as well as promoting phosphorylation of the T220 residue by MOM-4. In addition, we show that WRM-1 is essential for the translocation of the LIT-1 kinase complex to the nucleus, the site of its TCF substrate. To our knowledge, this is the first report of a MAP3K directly activating a MAPK by phosphorylation within the activation loop. This study should help uncover novel and as yet underappreciated functions of vertebrate β-catenin.
50
Garland, Michael A., Mitra C. Geier, Sean M. Bugel, Prarthana Shankar, Cheryl L. Dunham, Joseph M. Brown, Susan C. Tilton, and Robyn L. Tanguay. "Aryl Hydrocarbon Receptor Mediates Larval Zebrafish Fin Duplication Following Exposure to Benzofluoranthenes." Toxicological Sciences 176, no. 1 (May 8, 2020): 46–64. http://dx.doi.org/10.1093/toxsci/kfaa063.
Full textAbstract:
Abstract The aryl hydrocarbon receptor (AHR) mediates developmental toxicity of several xenobiotic classes including polycyclic aromatic hydrocarbons. Using embryonic zebrafish, we previously identified 4 polycyclic aromatic hydrocarbons that caused a novel phenotype among AHR ligands—growth of a lateral, duplicate caudal fin fold. The window of sensitivity to the most potent inducer of this phenotype, benzo[k]fluoranthene (BkF), was prior to 36 h postfertilization (hpf), although the phenotype was not manifest until 60 hpf. AHR dependency via Ahr2 was demonstrated using morpholino knockdown. Hepatocyte ablation demonstrated that hepatic metabolism of BkF was not required for the phenotype, nor was it responsible for the window of sensitivity. RNA sequencing performed on caudal trunk tissue from BkF-exposed animals collected at 48, 60, 72, and 96 hpf showed upregulation of genes associated with AHR activation, appendage development, and tissue patterning. Genes encoding fibroblast growth factor and bone morphogenic protein ligands, along with retinaldehyde dehydrogenase, were prominently upregulated. Gene Ontology term analysis revealed that upregulated genes were enriched for mesoderm development and fin regeneration, whereas downregulated genes were enriched for Wnt signaling and neuronal development. MetaCore (Clarivate Analytics) systems analysis of orthologous human genes predicted that R-SMADs, AP-1, and LEF1 regulated the expression of an enriched number of gene targets across all time points. Our results demonstrate a novel aspect of AHR activity with implications for developmental processes conserved across vertebrate species.