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1
Hammond, Christina Lindsey. "Pax3 and Pax7 in the zebrafish somite." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427989.
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Zalc, Antoine. "Study of Pax3 and Pax7 functions during the development of the mouse embryo." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066220.
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Mon travail de thèse a porté sur l'étude des mécanismes contrôlant la progression du cycle cellulaire et le devenir des cellules progénitrices dans différents tissus. Sortie du cycle cellulaire et différenciation cellulaire pendant la formation du muscle du membre Nous avons montré que la sortie du cycle cellulaire, régulée par les inhibiteurs de kinases cycline-dépendantes (CDKI) et la différentiation musculaire contrôlée par les facteurs myogéniques (MRF), peuvent être découplées génétiquement pendant la formation du muscle. Nous avons identifié une séquence régulant l'expression de CDKI, spécifique au muscle, activée par les MRF dans les myoblastes et réprimée par la voie Notch dans les progéniteurs, permettant de contrôler la balance entre amplification des progéniteurs et établissement du muscle squelettique. Contrôle de la croissance des dérivés de crête neurale craniale Bien que Pax3 et Pax7 soient essentiels pour la formation de la crête neurale, leurs rôles durant le développement craniofacial restent inconnus. À l'aide de mutants murins pour Pax3/7 présentant des fentes faciales, nous avons montré que ces défauts sont liés à la surexpression de la voie de signalisation régulée par le récepteur Aryl hydrocarbon (AhR, récepteur à la dioxine). L'augmentation de l'activité d'AhR pousse les cellules mésenchymateuses faciales hors du cycle cellulaire alors que son inhibition restaure la prolifération de ces cellules, permettant la fermeture de la face des mutants Pax3/7 et démontrant qu'une interaction entre une voie de signalisation impliquée dans la réponse au stress environnemental et les gènes régulés par Pax3/7 est nécessaire pendant le développement craniofaciaThis thesis aims to decipher how Pax3 and Pax7 transcription factors control cell cycle progression of progenitor cells in different tissues.Cell cycle regulation of Pax3+ myogenic progenitors during limb muscle developmentWe showed that cell cycle exit, mediated by the cyclin-dependent kinases inhibitors (CDKI), and muscle differentiation, controlled by the myogenic regulatory factors (MRF), can be genetically uncoupled during development. We dissected a functional interplay between Notch signalling and both MRF and CDKI activities, for maintaining the cycling status of the progenitor cells. Further, we identified a CDKI, muscle-specific DNA regulatory element, activated by the MRF in myoblasts but repressed by Notch signalling in progenitor cells, controlling the equilibrium between amplification of the progenitor pool and the establishment of functional muscle.Control of Pax3+ neural crest derivatives growth, and maintenance during craniofacial developmentAlthough studies showed Pax3 and Pax7 to be essential during early neural crest development, their role during craniofacial formation is unknown. Using Pax3/7 mutant mice displaying facial clefts, we uncovered that these defects are associated with an up-regulation of the Aryl hydrocarbon Receptor (AhR, the receptor to dioxin) signalling pathway. In Pax3/7 mutants, increased AhR activity drives facial mesenchymal cells out of the cell cycle, while inhibiting AhR rescues the cycling status of these cells and the facial closure of Pax3/7 mutants. Our results identify a molecular link between an environmental stress response pathway and a Pax3/7 downstream gene regulatory network during normal craniofacial development
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Wang, Wei Zhi. "The study of PAX3 and PAX7 genes and their potential roles in neuroblastoma." Thesis, Manchester Metropolitan University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263958.
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Zalc, Antoine. "Study of Pax3 and Pax7 functions during the development of the mouse embryo." Electronic Thesis or Diss., Paris 6, 2014. http://www.theses.fr/2014PA066220.
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Mon travail de thèse a porté sur l'étude des mécanismes contrôlant la progression du cycle cellulaire et le devenir des cellules progénitrices dans différents tissus. Sortie du cycle cellulaire et différenciation cellulaire pendant la formation du muscle du membre Nous avons montré que la sortie du cycle cellulaire, régulée par les inhibiteurs de kinases cycline-dépendantes (CDKI) et la différentiation musculaire contrôlée par les facteurs myogéniques (MRF), peuvent être découplées génétiquement pendant la formation du muscle. Nous avons identifié une séquence régulant l'expression de CDKI, spécifique au muscle, activée par les MRF dans les myoblastes et réprimée par la voie Notch dans les progéniteurs, permettant de contrôler la balance entre amplification des progéniteurs et établissement du muscle squelettique. Contrôle de la croissance des dérivés de crête neurale craniale Bien que Pax3 et Pax7 soient essentiels pour la formation de la crête neurale, leurs rôles durant le développement craniofacial restent inconnus. À l'aide de mutants murins pour Pax3/7 présentant des fentes faciales, nous avons montré que ces défauts sont liés à la surexpression de la voie de signalisation régulée par le récepteur Aryl hydrocarbon (AhR, récepteur à la dioxine). L'augmentation de l'activité d'AhR pousse les cellules mésenchymateuses faciales hors du cycle cellulaire alors que son inhibition restaure la prolifération de ces cellules, permettant la fermeture de la face des mutants Pax3/7 et démontrant qu'une interaction entre une voie de signalisation impliquée dans la réponse au stress environnemental et les gènes régulés par Pax3/7 est nécessaire pendant le développement craniofaciaThis thesis aims to decipher how Pax3 and Pax7 transcription factors control cell cycle progression of progenitor cells in different tissues.Cell cycle regulation of Pax3+ myogenic progenitors during limb muscle developmentWe showed that cell cycle exit, mediated by the cyclin-dependent kinases inhibitors (CDKI), and muscle differentiation, controlled by the myogenic regulatory factors (MRF), can be genetically uncoupled during development. We dissected a functional interplay between Notch signalling and both MRF and CDKI activities, for maintaining the cycling status of the progenitor cells. Further, we identified a CDKI, muscle-specific DNA regulatory element, activated by the MRF in myoblasts but repressed by Notch signalling in progenitor cells, controlling the equilibrium between amplification of the progenitor pool and the establishment of functional muscle.Control of Pax3+ neural crest derivatives growth, and maintenance during craniofacial developmentAlthough studies showed Pax3 and Pax7 to be essential during early neural crest development, their role during craniofacial formation is unknown. Using Pax3/7 mutant mice displaying facial clefts, we uncovered that these defects are associated with an up-regulation of the Aryl hydrocarbon Receptor (AhR, the receptor to dioxin) signalling pathway. In Pax3/7 mutants, increased AhR activity drives facial mesenchymal cells out of the cell cycle, while inhibiting AhR rescues the cycling status of these cells and the facial closure of Pax3/7 mutants. Our results identify a molecular link between an environmental stress response pathway and a Pax3/7 downstream gene regulatory network during normal craniofacial development
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Charytonowicz, Elizabeth. "The role of PAX3/PAX7-FKHR in mesenchymal stem cell myogenic differentiation and rhabdomyosarcomagenesis." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2011. https://ro.ecu.edu.au/theses/381.
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Rhabdomyosarcomas are soft tissue sarcomas (STS) that, while extremely rare in adults, are one of the most common neoplasms in children and adolescents. Rhabdomyosarcomas are presumed to be associated with the skeletal muscle lineage, although surprisingly, those tumors can be present in organs histologically lacking skeletal muscle, like prostate, urinary bladder or gallbladder. Pathologically, rhabdomyosarcomas are very heterogeneous tumors and can be divided into three major groups: alveolar rhabdomyosarcomas (ARMS), embryonal rhabdomyosarcomas (ERMS), which includes the botryoid subtype, and pleomorphic rhabdomyosarcomas. Besides clinicopathological differences, these tumors also differ at the molecular level. As in many other sarcoma types, ARMS are characterized by specific chromosomal translocations and almost 75% of cases show t(2;13) or t(1;13) translocations, involving PAX3-FKHR and PAX7-FKHR fusion genes respectively. These genetic events result in a molecular gain of function of the fusion protein, which is proposed to perturb the differentiation of muscle progenitor cells. Since PAX3/7-FKHR fusions result in rearrangements of PAX3/7 and FKHR genes, such that the PAX C-terminal domain is replaced by the potent FKHR transactivation domain, we sought to investigate the implications of this translocation on function and expression of wild type PAX3 and PAX7 Cterminal isoforms. This research identified functional differences between Pax3 and Pax7 Cterminal isoforms during myogenesis, and suggests that both Pax3 and Pax7 transcripts are required for commitment of cells to the myogenic lineage. More specifically, the Pax3c isoform may be required for terminal myogenic differentiation whereas the Pax3d isoform may be involved in undifferentiated cell maintenance and/or proliferation. Therefore, different levels of individual C-terminal isoforms of Pax3 and Pax7 in normal cells v may shift the balance between the undifferentiated and differentiated phenotype during muscle cell differentiation. In ARMS, this „balance‟ appears to be further disrupted and may lead to a block in terminal differentiation.
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Zalc, Antoine [Verfasser]. "Study of Pax3 and Pax7 functions during the development of the mouse embryo / Antoine Zalc." Berlin : Freie Universität Berlin, 2019. http://d-nb.info/1181097932/34.
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Mimault, Benoît. "Modifications géniques des cellules du tube neural : implication dans le développement myogénique des somites." Nantes, 2010. http://www.theses.fr/2010NANT2074.
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Dans l’embryogenèse la myogenèse se déroule dans les somites suite à l’activation des FRM et dépend pour un déroulement correct de toutes les structures qui ceinturent le somite. Hormis les FRM les facteurs de transcription Pax3 et Pax7 qui appartiennent à la même sous famille et sont exprimés dans le TN et les somites, sont impliqués dans la myogenèse. Leur influence sur les somites depuis le compartiment neural est peu documentée. Nous montrons que la suractivation neurale de Pax3 conduit à l’inactivation de l’expression des gènes de détermination moléculaire MyoD et Myf5 ainsi que du gène Wnt11 dans les somites. Celle de Pax7 induit uniquement la dérégulation de Wnt11 à laquelle s’ajoute celle de Sim1. La sous expression neurale de Pax3 n’a aucun effet concluant sur les somites, en revanche dans le cas d’inhibition neurale totale, Myf5 n’est plus activé dans le somite. La sous expression neurale de Pax7 n’a pas cet effet par contre là encore Sim1 et Wnt11 sont dérégulés. Il semblerait que les effets de Pax3 neural s’opèrent sur le somite épaxial (via Myf5, MyoD, Wnt11) ceux de Pax7 se situent à la fois dans le somite épaxial et hypaxial (via Wnt11 et Sim1). Nos résultats doivent faire admettre que Pax3 et Pax7 interfèrent depuis le TN sur la myogenèse somitique. Par ailleurs, nous induisons dans les cellules neurales l’expression ectopique de gènes impliqués dans la myogenèse épaxiale (MyoD, Wnt11) et hypaxiale (Sim1). A partir de l’ensemble de nos résultats nous proposons un nouveau schéma récapitulant les interactions moléculaires TN/somitesIn embryogenesis the skeletal myogenesis takes place in somites after the myogenic regulatory factor (MRF) activation. This process depends on environmental cues. Out of MRF, the transcription factors Pax3 and Pax7 which belong to the same factor family are also involved in myogenesis. They are both expressed in somites and neural tube. Their somitic influence from the neural tube is poorly documented. We demonstrate that the neural Pax3 upregulation leads to inactivation of the MRF MyoD and Myf5, and of the Wnt11 gene in the somites. The neural Pax7 upregulation only leads to Wnt11 and Sim1 misregulation. The neural downregulation of Pax3 has no effects about somites. When Pax3 is totally absent in neural tube through Pax3 deletion, Myf5 is no more activated in somites. The neural downregulation of Pax7 leads to the misregulation of Sim1 and Wnt11. It seems that the neural Pax3 acts on epaxial somite (via Myf5, MyoD, and Wnt11) and Pax7 on epaxial and hypaxial somite(via Wnt11 and Sim1). Our results must do accept that Pax3 and Pax7 influence somitic myogenesis from the neural tube. Otherwise we can induce in neural cells the ectopic expression of myogenic genes (MyoD, Wnt11, and Sim1). Consequently we propose a new scheme about the neural tube/somite interactions
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Maderer, Carmen [Verfasser], and Markus [Gutachter] Metzler. "Etablierung einer routinetauglichen PCR-Methode zur Charakterisierung genomischer PAX3/FKHR bzw. PAX7/FKHR Bruchpunkte bei Patienten mit alveolärem Rhabdomyosarkom / Carmen Maderer ; Gutachter: Markus Metzler." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2017. http://d-nb.info/1148105158/34.
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Torban, Elena. "Functions of PAX2 and PAX8 genes during kidney development." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36844.
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The 9 PAX genes constitute a family of developmental transcriptional regulators characterized by a highly conserved "paired-box" domain. Mutations in 6 of the 9 PAX genes result in autosomal dominant congenital malformations in mice and in humans. PAX2 transcripts are detected in the CNS, throughout the genitourinary tract, eye and ear. In humans, mutations of PAX2 cause Renal-Coloboma Syndrome (RCS), a constellation of renal anomalies, eye defects and, less frequently, hearing loss and mild CNS manifestations. Homozygous PAX2 mutations in mice cause complete renal agenesis and perinatal death. PAX8 transcripts are found in the CNS, kidney and thyroid glands. PAX8 mutations cause congenital thyroid hypoplasia. No renal defects have been detected either in human or murine PAX8 mutants.In spite of considerable information about PAX2 and PAX8 genes, their precise functions in development are poorly understood. This project was aimed at elucidating the functions of PAX2 and PAX8 in nephrogenesis and is subdivided into two parts: mutational screening of the PAX8 gene (Chapter 4) and delineation of the role of PAX2 in developing kidney (Chapters 5--7). The latter evolved into the major portion of this work.
Familial juvenile nephronophthisis (NPH1) is a rare disease characterized by multiple small cysts at the cortico-medullary junction and end-stage renal failure in pediatric populations. Because of its proximity to the disease locus, we considered PAX8 a candidate gene for NPH1. During analysis of PAX8 exons from patients, we identified a rare non-conservative polymorphic amino acid change, but found no causative mutations. Subsequently, other groups isolated the novel NPH1 gene. Following reports that PAX8 knockout mice have no obvious renal anomaly, we considered the possibility that PAX8 mutations might, nevertheless, affect proximal tubule function. In patients with thyroid hypoplasia and proven PAX8 mutations we found no aminoaciduria, indicating that haploinsufficiency for PAX8 does not alter tubular transport function.
In order to define PAX2 function in the two primordial cell lineages of developing kidney (induced metanephric mesenchyme and ureteric epithelium), we used both a cell culture approach and an in vivo PAX2 mutant mouse model (1Neu). We demonstrated that PAX2 plays a dual role. In mesenchymally-derived HEK293 cells expressing regulatable exogenous PAX2, we showed that PAX2 is responsible for expression of genes involved in differentiation of mesenchyme. Contrary to one published hypothesis, we found that PAX2 does not affect cell division. In ureteric epithelium, however, PAX2 plays a different role, serving as a survival factor, critical for sustaining the ureteric bud stem cell population. Attenuation of PAX2 dosage (1Neu mouse mutants or collecting duct cells transfected with an antisense PAX2 vector) results in increased apoptosis. We demonstrate that the primary renal defect in RCS is reduced nephron number associated with excessive apoptosis and simplified branching of the ureteric bud. We hypothesize that arborization of the uretric bud requires accumulation of sufficient stem cell mass to allow the next round of branching---possibly by lifting the branch point beyond a putative local inhibitory field.
In summary, we establish that inactivation of PAX8 gene expression does not disturb normal kidney development and function. Conversely, PAX2 plays a crucial dual role in the two primordial kidney cell lineages: being a differentiating factor in mesenchyme and a survival factor in ureteric epithelium.
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Zhang, Hong. "Regulation of Skeletal Muscle Development And Differentiation by Ski." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1226938149.
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MacDonald, Rachel Elizabeth. "Characterisation of Pax2 and Pax6 during forebrain and eye development in the zebrafish." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362454.
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Kelly, Michelle Anne. "Molecular regulation of thymic epithelial lineage specification." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/10433.
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The genetic mechanisms underlying the specification of thymic epithelial (TE) lineage cells are poorly understood. Foxn1 is an early specific marker of thymic epithelial cells (TECs) in the third pharyngeal pouch (3PP) and is required for development of all mature TE lineage cells but does not specify the TE lineage. The upstream regulators of Foxn1 are currently unknown, however evidence points to a potential role for Pax1 and Pax9. While the thymus phenotypes of the Pax1-/- and Pax9-/- mutant mice have been investigated in detail and TECs in these mice are known to express Foxn1, the possibility of functional redundancy exists and the compound mutants of these genes have not been studied. Therefore, the aim of this thesis was to test the hypothesis that Pax1 and Pax9 are required for TE lineage specification and regulation of Foxn1 expression. This hypothesis was addressed by analysis of thymus development and TEC function in Pax1/Pax9 compound mutant mice. The data presented in this thesis indicates that prenatally, Pax1 and Pax9 cooperatively regulate thymus organogenesis, such that the size, structure and location of the thymus is affected in a Pax1/Pax9 gene dosage-dependent manner, and the Pax1unex/unexPax9lacZ/lacZ embryo is functionally athymic. Furthermore, they establish that the thymic rudiment of Pax1unex/unexPax9lacZ/lacZ embryos does not express Foxn1, establishing that Pax1 and Pax9 are required together for the initiation of Foxn1 and suggesting they are required to specify the TEC lineage. Postnatally, enlarged blood vessels observed in the Pax1unex/unex thymus suggested a role for Pax1 in vascularisation of the thymus. In addition, the effect of loss of one or more Pax1/Pax9 alleles on the expression of Foxn1 and other genes known to regulate TEC development or function was assessed. These data demonstrate that Pax1 and Pax9 co-operate to regulate Foxn1 in a dosage-dependent manner. Furthermore, Pax1 and Pax9 appear to negatively regulate both Hoxa3 and Vegfa, providing a possible explanation for the enlarged blood vessels in the postnatal Pax1unex/unex thymus. Finally, an inducible and reversible recombinase-mediated cassette exchange system that will allow the knockdown of Pax1 and Pax9 at defined time points during development has been established, that has the potential to test the function of these genes during thymus organogenesis and in the postnatal thymus.
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Buisson, Isabelle. "Etude des rôles de pax2 et pax8 dans la mise en place du pronéphros chez le xénope." Paris 6, 2013. http://www.theses.fr/2013PA066232.
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Chez Xenopus laevis, le pronéphros est le rein fonctionnel au stade larvaire. Il est constitué d’un seul néphron, composé du glomus, du tubule et du tube collecteur. Le mésoderme pronéphrique est spécifié au stade jeune neurula, il exprime les gènes Pax8, lhx1 et osr1/2. L’ébauche du pronéphros se forme au stade jeune bourgeon caudal. Puis, le tubule s’épithélialise et le glomus se différencie. Au cours de ma thèse, j’ai analysé les rôles des facteurs de transcription Pax2 et Pax8 au cours de la formation du pronéphros. Au stade têtard, les pertes de fonction Pax2 ou Pax8 conduisent à la formation d’un œdème, conséquence d’une malformation rénale. Au stade bourgeon caudal âgé, les morphants Pax8 présentent une diminution sévère de l’expression des gènes marqueurs de l’ensemble du tubule, tandis que seuls les marqueurs proximaux sont affectés dans les morphants Pax2. Contrairement aux morphants Pax2, l’ébauche du pronéphros est absente dans les morphants Pax8. Une expansion du domaine d’expression des précurseurs endothéliaux et hématopoïétiques est observée dans les morphants Pax8, suggérant un changement d’identité de certains précurseurs du pronéphros. Au stade neurula, Pax8 est requis pour l’expression de vhnf1, mais pas pour celle de lhx1 et osr1/2. La perte de fonction Pax8 conduit également à une modification de l’expression de dvl1 et sfrp3 ainsi qu’à une diminution de la prolifération dans le champ pronéphrique qui peut être restaurée par l’activation de la voie de signalisation Wnt/bcatenine. Pax8 joue un rôle majeur dès la mise en place des précurseurs du pronéphros, tandis que Pax2 joue un rôle plus tardif sur la différenciation du tubuleIn Xenopus, the pronephros is the functional larval kidney. It comprises 3 components: the glomus, a segmented and a collecting tubule. Specification of the pronephric mesoderm is achieved at the early neurula stage. Pax8, lhx1 and osr1/2 are the earliest markers identified in the presumptive pronephric field. At the early taibuld stage, the pronephros anlage is formed. Then, epithelialisation of tubule occurs and the glomus differentiates to form a functional nephron at tadpole stage. I have analyzed the role of the transcription factors, Pax2 and Pax8 in pronephros formation. At tadpole stage, knock down of Pax2 or Pax8 leads to a severe edema as a consequence of kidney malformations. At the late tailbud stage, morphants Pax8 show a decreased expression of the tubule markers while only the proximal markers are affected in Pax2 morphants. Pronephros anlage is formed in Pax2 morphants but is absent in Pax8 morphants. An expansion of the expression domain of endothelial and hematopoietic markers genes in the dorso-lateral plate is also observed, suggesting that some pronephric precursors may change fate. Pax8 is required for vhnf1 but not for lhx1 and osr1/2 expression in the kidney field at the early neurula stage. At this stage, the loss of Pax8 leads to a modification of dvl1 and sfrp3 expression, and a decreased of cell proliferation in the kidney field, which can be rescue by wnt/bcatenin pathway. Pax8 is required for pronephric tubule fate specification while Pax2 is required for tubule differentiation
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Li, Hongmei. "An Investigarion of PAX3 Isoforms (PAX3c, e AND g) in C2c12 Myoblasts." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492771.
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White, Robert B. "The developmental function of Pax7 : chromatin-immunoprecipitation discovery of Pax7 target genes." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2007. https://ro.ecu.edu.au/theses/279.
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Pax7 plays critical roles in development of brain, spinal cord, neural crest and skeletal muscle. As a sequence-specific DNA-binding transcription factor, the direct functional role played by Pax7 during development is the selection of target genes. To date, an accurate description of the function of this transcription factor has not been obtained through an understanding of its target genes. To elucidate the direct developmental functions of Pax7, this research has sought to identify genes targeted by Pax7 during mouse embryonic development.
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Plaza, Serge. "Étude de la régulation transcriptionnelle du gène Pax-QNR/Pax6, un gène essentiel pour la formation des yeux." Lille 1, 1995. http://www.theses.fr/1995LIL10068.
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De nombreux progrès dans la compréhension des mécanismes moléculaires qui régissent la différenciation cellulaire ont pu être réalisés grâce a l'isolement de gènes du développement. Le laboratoire, qui s'intéresse aux mécanismes de prolifération et de différenciation de la neurorétine aviaire, a isolé et caractérisé un gène, dénommé Pax-QNR, spécialement exprimé dans ce tissu. Ce gène, qui est l'homologue du gène Pax6 de souris, code un facteur de transcription essentiel pour le développement de l'oeil et du système nerveux central chez la souris et l'homme. Afin d'étudier la régulation transcriptionnelle du gène Pax-QNR, les régions régulatrices de la transcription de ce gène ont été isolées et caractérisées. Deux régions de promotion, appelées P0 et P1, dirigent la synthèse des ARNm. Au cours du développement de la neurorétine les ARNm initiés à chacun des promoteurs sont exprimés dans les mêmes couches cellulaires mais à des taux différents ce qui suggère un contrôle transcriptionnel spécifique pour chaque promoteur. Alors que le promoteur P1 peut être considéré comme un promoteur constitutif des territoires d'expression du gène Pax6, le promoteur P0 apparaît comme un promoteur inductible et serait spécifique des cellules neuronales. Une séquence activatrice intragénique située 7. 5 Kbp en aval du promoteur P0 et fonctionnant spécifiquement dans la neurorétine a été caractérisée. Cet activateur augmente l'activité du promoteur P0 mais pas celle du promoteur P1 et constitue donc un élément de régulation différentiel de chacun des promoteurs. De plus, cet activateur est régulé au cours du développement de la neurorétine. Enfin, la protéine Pax-QNR de 46 kDa ainsi que le produit du proto-oncogène c-myb, se fixent sur les séquences promotrices et régulent positivement le gène Pax-QNR.
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三瀬, 武史. "Pax1/9から重複で生じたPax1とPax9の発現領域・機能・シスエレメントの硬骨魚類における進化." 京都大学 (Kyoto University), 2005. http://hdl.handle.net/2433/144425.
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Rosembert, Tabitha. "Myst1 Acetyltranferase Regulates Pax7 Function." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37376.
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Pax7 is essential for the function of muscle satellite cells. It was previously determined that Pax7 methylation is essential for its transcriptional activity and function in satellite cells. We investigated whether Pax7 displays other post-translational modifications playing a role in its function. By mass spectrometry using immunoprecipitated FLAG-Pax7, we identified two lysine residues (K105 and K193) within the Pax7 protein that are acetylated. Pax7 transcriptional activity was monitored using a luciferase reporter under the control of Myf5, a Pax7 target gene. Treatment with Trichostatin A, a histone deacetylase inhibitor, increased significantly luciferase activity, but this activity was progressively loss when the created Pax7 mutants (K105R, K193R) were introduced. This suggests that acetylation plays a role in Pax7 transcriptional activity. To identify the acetyltransferase modulating Pax7 activity, we used a candidate approach. Myst1 is expressed in muscle satellite cells. Myst1 is known for its interaction with Wdr5 and MLL1/2, a known Pax7 partner. We detected an interaction between Pax7 and Myst1 by co-immunoprecipitation in fibroblasts and in primary myoblasts. Myst1 knockdown decreases Pax7 acetylation status suggesting Myst1 as Pax7’s acetylase. Myst1 siRNA knockdown negatively impacts many Pax7’s target genes as well as primary myoblast proliferation. Moreover, primary myoblasts treated with siMyst1 express higher levels of MyoD. In satellite cells Myst1 reduction through siRNA knockdown significantly reduces satellite cells progenitor expansion as well as increases MyoD expression. In all, Myst1 modulating Pax7 activity through acetylation represents a novel mechanism in muscle stem cell biology.
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Medic, Sandra. "PAX3 and cutaneous malignant melanoma." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2006. https://ro.ecu.edu.au/theses/341.
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Cutaneous Malignant Melanoma (CMM) is the most aggressive form of skin cancer, with high mortality rate in patients with metastatic spread. The focus of recent research has been to find molecular markers of melanoma that can be used to detect metastatic cells in the blood of patients with CMM and to assist in diagnosis and staging as well as to predict the outcome of the disease. PAX3, a transcription factor encoding gene that regulates melanocyte migration, proliferation and differentiation during development is found to be highly expressed in melanomas and melanoma cells, particularly its alternate transcript PAX3d. Therefore, the aim of this study was to establish an assay that can be used to detect occult melanoma cells in peripheral blood of patients with CMM and to assess PAX3d as a melanoma cell marker.
We used staged formalin-fixed paraffin-embedded tissue and metastatic lymph node tissue to assess the expression of PAX3 transcripts in primary and metastatic melanoma tissue as well as in naevi and normal skin. Although problematic we were able to establish a technique for isolation of total RNA from archival formalin-fixed tissue slides. Furthermore, we perfected blood collection procedures and methods of total RNA isolation from peripheral blood. We also demonstrated that real time qRT-PCR provides a significantly higher marker detection rate relative to conventional gel-based RT-PCR and therefore suggest its use as a more sensitive and accurate detection method.
Analysis of PAX3 expression in peripheral blood of patients diagnosed with CMM showed significantly higher marker expression frequency in patient blood samples in contrast to no expression in blood from healthy volunteers. Results also showed that the alternate transcript PAX3d was detected at significantly higher frequencies in peripheral blood of melanoma patients than the PAX3c alternate transcript. Moreover PAX3d was more frequently expressed in patients diagnosed with metastatic disease compared to those diagnosed with in-situ and invasive melanoma.
Frequent expression of PAX3d in patients with in-situ melanoma even after more than one year since diagnosis was interesting, and suggests the presence of circulating melanoma cells even at this early stage of the disease. Since recent studies have found that melanoma cells with high metastatic potential have a different gene expression signature compared to highly proliferative cells with low metastatic potential, it is still to be clarified whether PAX3d is a marker of metastatic cells with low or high metastatic potential. Nevertheless, results presented here show that PAX3d is a sensitive and useful marker of melanoma cells in peripheral blood of melanoma patients.
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Fenby, Benjamin. "Transcriptional targets of Pax3 during development." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/28003.
Full textAbstract:
Transcription factors play multiple and important roles during embryonic development. The Pax gene family have been shown to be essential in these processes, and mutations which abrogate their function disrupt the development of a range of embryonic tissues. One member of this family, Pax3, is characterised by a semidominant mutant phenotype and is involved in the proper formation of the brain, central and peripheral nervous system, hypaxial musculature, and cardiac outflow vessels. Pax3 is a transcription factor and its biological role involves the binding of specific sequences in genomic DNA to regulate the expression of a set of target genes. Defects observed in animals harbouring a mutation in Pax3 are assumed to arise from the misregulation of the transcriptional targets of this gene. In dissecting the precise biological function of Pax3, it is important to differentiate between primary and secondary phenotypes in the mutant animal; specifically, between defects caused by the direct misregulation of Pax3 targets and those generated by the compounded knock -on effects of a dysfunctional master -regulator such as Pax3. A simple comparison of expression profiles between wild type and mutant animals, using microarray or differential display based methodologies, would not achieve this aim. To date, no attempt to perform a comprehensive screen for direct Pax3 targets in development has been performed. This thesis presents a development of the tools necessary to perform the task of identifying direct targets of Pax3 in vivo. Firstly, two candidate genes for direct Pax3 regulation are considered, Wntl and Pax7. These candidates are implicated from previous work on Pax3 although no direct transcriptional link has ever been established. Firstly, differences in the expression of these genes between the Pax3 mutant and wild type embryos is quantitatively analysed. In the case of Pax7, little work had been performed to identify the regulatory elements controlling its expression in the mouse. Described here is a series of experiments mapping the 5' end of the transcript, the delineation of a putative promoter region and the identification and cloning of a highly conserved enhancer element within the first intron. The Wntl regulatory elements have been well described elsewhere. A series of experiments are then performed to confirm the interaction between these regulatory regions and Pax3 and the identification and testing of specific Pax3 binding sites is reported. To confirm these interactions in vivo, chromatin immunoprecipitation, using a novel mono -specific anti -Pax3 antibody designed for the purposes of this thesis, is used. This technique, having been verified on these two direct Pax3 targets in this way, could then be used to screen for novel direct targets of Pax3 regulation in vivo and in the wild type; expanding our understanding of the pathways and developmental function of this gene in future.
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Blake, Judith A. "Pax3 expression in cutaneous malignant melanoma." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2005. https://ro.ecu.edu.au/theses/667.
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This research investigated the repercussions of aberrant PAX3 re-expression in cutaneous malignant melanoma (CMM). The transcription, factor encoded by PAX is amongst the first expressed in the embryo, with a principal role in the development of the melanocytic lineage. We theorised that abnormal re-expression of PAX3, consistently observed in CMM as compared to normal melanocytes, is linked to progression of CMM. Previous studies have stated that expression profiles of PAX3 in CMM demonstrate predominant generation of a protein encoded by exons 1-9 (PAX3D) utilizing cryptic splice sites in post-transcriptional pre-mRNA splicing. By contrast, normal human skin demonstrates low level generation of PAX3C (encoded by exons 1-8). Using RT-PCR based techniques and immunohistochemistry, we present original evidence of Pax3c, Pax3d mRNA and protein expression in normal murine embryogenesis and melanogenesis, identifying a conserved role for the Pax3d protein in transcriptional regulation of the murine melanoblast. Furthermore, to identify a role for Pax3 in adult skin, we used a reliable time-scale for the strict coupling of melanogenesis to active hair regrowth; Pax3c and Pax3d expression profiles were assessed during depilation experiments which induced murine malanocytic stem cells to proliferate, migrate into the hair cortex and differentiate in order to produce melanin for new hair. Results indicate that strict temporal expression of Pax3d may be linked to either melanoblast proliferation or migration in early melanogenesis thus supporting a possible role for PAX3D in the tumourigenesis of CMM.
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Wang, Weiguang. "The study of the oncogenic effect of PAC3, PAX3-FKHR and IGF-II genes in rhabdomyosarcoma and medulloblastoma." Thesis, Manchester Metropolitan University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243719.
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Fang, Wen-Hui. "The oncogenic role of PAX3 in neuroblastoma." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521579.
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Cooper, Simon T. "PAX6 protein-protein interactions." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29070.
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The gene PAX6 is located on chromosome 11 (11p13) and encodes a transcription factor (PAX6) that is expressed early in development. The PAX6 protein is expressed in the developing eye, regions of the brain, central nervous system (CNS), nasal epithelium and pancreas. PAX6 is best known for its role eye development with heterozygous mutations causing congenital ocular malformations. However, it must be remembered that PAX6 has multiple functions in the brain including specification of neuronal subtypes and axon guidance. There is growing understanding of the role of PAX6 as a transcription factor during development, and many of its DNA targets have recently been defined. However, almost nothing is known about the proteins with which PAX6 interacts. In the initial stage of my research I identified a conserved region consisting of the final 32 amino acids of the PST (proline, serine and threonine rich) domain of PAX6. Based on sequence homology and secondary structure predictions I classed this region as a novel domain, the ‘C terminal domain’. Next I used the yeast 2-hybrid system to investigate possible PAX6 protein interactions. By screening a mouse brain cDNA library with the C terminal domain and whole PST domain, I identified three novel and interesting interactors, HOMER3, DNCL1 and TRIM11. I re-confirmed these interactions in a pairwise manner using the yeast 2-hybrid system, and I showed that the C terminal domain was vital for the interactions between PAX6 and HOMER3 or DNCL1. Furthermore, certain C terminal mutations that are known to cause ocular malformations in patients are also sufficient to reduce or abolish these interactions. I attempted to further characterise the interactions by co-immunoprecipitation. However, this was not possible due to technical difficulties.
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Paixão, Côrtes Vanessa Rodrigues. "PAX9 : uma ferramenta evolutiva?" reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2008. http://hdl.handle.net/10183/29978.
Full textAbstract:
Um dos maiores objetivos na ciência atual é poder relacionar alterações nos genes a mudanças nas morfologias de organismos multicelulares. Além disso, é importante poder determinar se estas modificações foram obras do acaso ou se a seleção natural teve um papel central moldando a forma e o tamanho das criaturas vivas. A busca por nutrientes e sua utilização é uma das questões mais básicas para a sobrevivência de uma espécie. Em mamíferos a diversificação e especialização dos dentes para triturar, rasgar e mastigar diferentes tipos de comida possibilitou um incremento na geração de energia e representou uma inovação chave para a sobrevivência deste grupo. No presente estudo foi investigado o gene PAX9, que codifica um fator de transcrição chave no desenvolvimento da dentição de mamíferos. Para 125 indivíduos de origem ameríndia foi seqüenciado o exon 3 (138 pb), conjuntamente com as regiões intrônicas flanqueadoras 5´e 3´(232 pb e 220 pb, respectivamente) e os dados integrados com a informação disponível para a mesma região de 115 indivíduos de diferentes origens geográficas. Além disso, os exons 2, 3 e 4 (627 pb, 138 pb e 240 pb respectivamente) foram seqüenciados do DNA de 25 espécies de mamíferos e agrupados com os dados disponíveis de mais 29 espécies. Em humanos, o polimorfismo Ala240Pro possui uma distribuição variada entre os Ameríndios da América do Sul e está presente em Esquimós, Asiáticos e Europeus, mas não está presente entre os Afro-Americanos. O panorama que surge é que provavelmente a partir da saída da África a freqüência da mutação Ala240Pro aumenta, sendo possivelmente selecionada positivamente, o que pode estar relacionado à agenesia do terceiro molar, ou ainda, estar associado a genes conectados a adaptações ao frio. Com a chegada dos Ameríndios a regiões equatoriais, outro cenário parece dominar a evolução do exon 3, seja pela perda inicial da possível vantagem adaptativa, ou por causa da ação da deriva genética amplamente documentada nestas populações. Provavelmente em algum momento na história destas populações, fatores casuais poderiam ter sido preponderantes às restrições funcionais da proteína. Em geral, há uma maior variabilidade em nível de aminoácidos no exon 3 considerando todos os mamíferos estudados quando comparada com a do exon 2, ficando o exon 4 numa posição intermediária. O exon 3 seria um exemplo notável de uma situação que conferiria “evolvabilidade” ao PAX 9.One of the main goals in science today is to establish the relation between gene changes and variations in the morphologies of multicellular organisms. In addition, it is important to determine if these changes were randomic or whether natural selection had a central role shaping the form and size of living beings. Searching for nutrients and its use is one of the most basic issues for a species survival. In mammals teeth diversification and specialization to grind, tear and chew different types of food were a key innovation that allowed an increase in the generation of energy and in the survival of this group. In this study an investigation was performed in the Paired box gene 9 (PAX9), which codes for a transcription factor that was a key factor in the development of mammal dentition. A total of 125 persons from Amerindian populations were studied by sequencing the PAX9 gene exon 3 (138 base pairs) as well as its 5´and 3´flanking intronic segments (232 bp and 220 bp, respectively) and the data integrated with the information available for the same genetic region from 115 individuals of different geographical origins. Moreover, exons 2, 3 and 4 (627 bp, 138 bp and 240 bp, respectively) were sequenced from DNA of 25 mammalian species and the results combined with the data available from other 29 additional species. In humans, the Ala240Pro polymorphism has a varied distribution among the South American Amerindians and is present in Eskimos, Asians and Europeans, but it is not present among Afro-Americans. The pattern that emerges is that probably starting with the out-Africa migration, and possibly as a result of positive selection, the Ala240Pro mutation frequency increased, that could be related to third molar agenesis or an associated gene connected to cold adaptation. With the Amerindian arrival again in equatorial regions, another pattern seems prevalent in exon 3 evolution, either due to the loss of a possible initial adaptive advantage, or to the action of genetic drift, widely documented in these populations. Probably at some point in the history of these populations, random factors could have been dominant despite the protein functional restrictions. In a general way, there is a greater variability at the amino acid level in exon 3 of all mammals considered when compared to exon 2, exon 4 occupying an intermediary position. Exon 3 would be a remarkable example of a condition that would confer PAX9 evolvability.
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Medic, Sandra. "New perspectives on melanoma: The role of PAX3." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2011. https://ro.ecu.edu.au/theses/414.
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Background: Cutaneous melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 is critical for the proper development of neural crest lineages including melanocytes. Melanocytic cells show continued PAX3 expression from melanoblast formation in the neural crest to their differentiation into melanocytes. While many studies clarify the importance of PAX3 in embryonic development of melanocytes, less well understood, and more perplexing, is the continued PAX3 expression in adult skin melanocytes. By contrast PAX3 is frequently found in melanomas and naevi, and its expression correlates with melanoma staging. In this study we explore the multiple roles of PAX3 in melanocyte genesis and melanoma progression. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during embryonic development, it is not clear if these same functions are maintained in adult melanocytes or melanoma cells. Drawing on evidence from development, we propose here a more encompassing theory that PAX3 is a key regulator of the myriad steps in melanocytic cell determination and function. We discuss the possibility that these roles may be accomplished by differential association with cofactors, via alternate transcripts or posttranslational protein modification(s). Moreover, we consider its possible roles in melanoma and provide a comprehensive consideration of the significance of PAX3 expression in melanoma.
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SIRABELLA, DARIO. "PAX3 mutant mesoangioblasts are defective in myogenic differentiation." Doctoral thesis, La Sapienza, 2005. http://hdl.handle.net/11573/917414.
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Teichler, Sabine. "Bedeutung der Homöodomäne des Transkriptionsfaktors Pax6 für die Aktivierung des Glukagon-Gens durch Pax6." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972733922.
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Sobolewska, Adrianna. "Wpływ stymulacji embriogenezy światłem i temperaturą na proces miogenezy u kurcząt." Rozprawa doktorska, Uniwersytet Technologiczno-Przyrodniczy w Bydgoszczy, 2015. http://dlibra.utp.edu.pl/Content/852.
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Celem badań jest ocena wpływu monochromatycznego światła barwy zielonej w dwóch różnych cyklach- zastosowanego między 1. a 18. dniem embriogenezy oraz podwyższonej temperatury lęgu między 156. a 18. dniem embriogenezy na masę ciała i miogenezę mięśnia piersiowego kurcząt brojlerów, wyrażoną jego masą, grubością włókien mięśniowych i liczbą komórek satelitowych (Pax7⁺) w 1., 4. i 8. dobie życia
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Minchin, James. "Pax3 genes drive cell fate choice in tissue-restricted progenitors." Thesis, King's College London (University of London), 2009. https://kclpure.kcl.ac.uk/portal/en/theses/pax3-genes-drive-cell-fate-choice-in-tissuerestricted-progenitors(746b8b18-c26e-49ac-aac4-835074e198fa).html.
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Dude, Carolynn Marie. "Pax3 and the development of the avian ophthalmic trigeminal placode." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612069.
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Wang, Qiuyu. "An investigation of alternative isoforms of the transcription factor PAX3." Thesis, Manchester Metropolitan University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418123.
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Palmer, A. J. "Cellular and molecular mechanisms underlying Pax3-related neural tube defects." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1469295/.
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The neural tube is the developmental precursor of the central nervous system (CNS). Neural tube defects (NTDs) are among the commonest birth defects, affecting approximately 1 in 1000 pregnancies. They occur when the neural tube fails to close completely during neurulation, and result in an open region of the CNS. Spina bifida is an NTD affecting the spinal region, and it can lead to lifelong disability, including incontinence, motor difficulties, and paralysis below the level of the lesion. Exencephaly is an NTD affecting the cranial region, and is not compatible with life. Splotch mice carry a mutation in the Pax3 gene which leads to a functionally null Pax3 protein. Pax3 is important in the development of a number of tissues, and mutant embryos have defects in muscle development, and neural crest-derived tissues, such as the heart, peripheral nervous system and melanocytes. Additionally, embryos develop NTDs; they demonstrate spina bifida with complete penetrance and exencephaly with partial penetrance. The cellular mechanism behind the development of NTDs in Splotch embryos is not well understood. However excess apoptosis, premature neuronal differentiation, and reduced proliferation in the neural tube have all been proposed as potential causes. Furthermore, research has suggested a potential link between Pax3 and canonical Wnt signalling. The aim of this research was to study cellular defects in Splotch mice which are potentially causative of NTDs, and also to study the interaction between Pax3 and canonical Wnt signalling. It was found that excess apoptosis and premature neuronal differentiation are not causative of spina bifida in Splotch mice. However, reduced proliferation is present in the neural tube, and may be causative. Additionally, β-catenin loss- and gain-of-function mutations were used to study interaction between Pax3 and canonical Wnt signalling. β-catenin loss-of-function reduces Pax3 expression, and β-catenin gain-of-function worsens NTDs in Pax3 mutant embryos, whereas loss-of-function partially rescues exencephaly, but not spina bifida, in these embryos. β-catenin gain- and loss-of-function both also worsen neural crest defects in Pax3 mutant embryos. Therefore, Canonical Wnt signalling interacts with Pax3 during development, and affects the cranial and spinal regions of the neural tube differently. In summary, Pax3 mutation results in a number of defects in developing embryos, including NTDs and neural crest defects. Cellular processes have been studied in this research to identify abnormalities which could be causative of these defects, and a potential molecular link between Pax3 and the canonical Wnt signalling pathway has been identified, which could contribute to the observed phenotype.
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Mashud, Ahmed Abdallah. "Down-regulation of PAX3 gene expression in rhabdomyosarcoma and melanoma." Thesis, Manchester Metropolitan University, 2014. http://e-space.mmu.ac.uk/332146/.
Full textAbstract:
The PAX3 gene as a member of the paired homeodomain family of transcription factors plays a crucial role during embryonal development by regulating the early development of neural structures, derivatives of the neural crest and skeletal muscles. Following embryonal development, the PAX3 expression is switched off. Mutations in the PAX3 gene are commonly associated with Waardenburg’s syndrome and in Craniofacial-hand syndrome. Aberrant re-expression of PAX3 after embryogenesis plays a key role in the onset, growth, survival and progression of rhabdomyosarcoma, melanoma and neuroblastoma. Alternative splicing of PAX3 results in seven transcript variants (PAX3a, PAX3b, PAX3c, PAX3d, PAX3e, PAX3g and PAX3h), the interactions of which with other downstream targets, make it difficult for manipulation and the development of potent chemotherapeutic regimens to effectively treat malignant tumours including rhabdomyosarcoma, melanoma and neuroblastoma which have unfavourable prognostic outcomes. This research was aimed at down-regulating PAX3 gene expression in human rhabdomyosarcoma and melanoma cell lines, subsequently identifying the downstream target genes of PAX3 and determining the effects on cell growth and survival. The expression of PAX3 in human rhabdomyosarcoma and human melanoma cell lines was significantly down-regulated using novel pre-designed PAX3 small interference RNA molecules, at a final concentration of 0.5μM in an in vitro transient transfection. The three prime Affymetrix microarray analyses showed more than a four-fold and a two-fold down-regulation of PAX3 gene expression in the human JR1 embryonal rhabdomyosarcoma and RH30 alveolar rhabdomyosarcoma cell lines respectively, whilst in the human A375 melanoma cell line, over an eight-fold down-regulation of PAX3 expression was demonstrated relative to negative control cells. A quantitative RT-PCR analysis, which was used in validating results of the Affymetrix array, confirmed the knockdown of PAX3 in both human rhabdomyosarcoma and melanoma cell lines. A semi-quantitative RT-PCR analysis of gene expression revealed at least 90% down-regulation of all PAX3 variant expression in JR1, RH30 and A375 cell lines relative to negative controls cells. Higher levels of gene silencing were observed in the JR1 cell line than in either RH30 or A375 cell lines. Western blotting analysis, which quantified the level of PAX3 gene knockdown, indicated a 98%, 92% and 90% reduction of PAX3 protein in JR1, RH30 and A375 cell lines respectively. This down-regulation of PAX3 expression significantly inhibited tumour cell growth, proliferation, migration, adhesion, invasion, and induced apoptosis of JR1, RH30 and A375 cell lines in vitro. These results were explainable by the particular genes that were up- or down-regulated by PAX3, which were correlated with the microarray results and the quantitative RT-PCR experiments. The expression of PAX3 gene has been previously demonstrated to promote tumourigenesis of rhabdomyosarcoma and melanoma. Results of this present study suggest that down-regulation of PAX3 might inhibit the progression of rhabdomyosarcoma and melanoma and PAX3 thus could be a suitable target for the development of potent chemotherapy. Silencing of PAX3 in these cell lines resulted in the alteration of expression of a host of downstream target genes, which PAX3 uses in the modulation of cellular activities, including cell growth, proliferation, migration, adhesion, metastatic invasion and apoptosis of the rhabdomyosarcoma and melanoma cell lines.
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Moore, S. J. "The regulatory logic of Pax3 expression in the neural tube." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1370636/.
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The development of complex tissues is dependent on the specification and maintenance of distinct transcriptional identities within populations of equivalent progenitors. In the vertebrate neural tube, progenitor identity is specified by the spatially organised expression of transcription factors within the dorso-ventral (DV) axis of the tissue. A series of selective cross-repressive interactions between transcription factors expressed in adjacent domains forms the basis of a gene regulatory network (GRN), which acts to define and maintain the boundaries between progenitor populations. Pax3 is a key member of the neural tube GRN that is transcribed throughout the dorsal domains of the spinal cord and exhibits a ventral boundary of expression at the level of the sulcus limitans. The regulatory mechanisms that induce Pax3 transcription in neural progenitors and subsequently produce a sharp ventral boundary of gene expression are poorly understood. Using a genetic lineage tracing strategy in mice, we show that the position of the Pax3 expression domain is established within the neural plate and subsequently maintained throughout spinal cord development. Additionally, we demonstrate that V0 interneuron progenitors transiently express Pax3 during their early development. We employ a comparative genomics based approach to investigate the molecular basis of Pax3 transcription, revealing several novel enhancers associated with the locus. Functional dissection of an early central nervous system (CNS) specific enhancer supports the role of the Wnt signaling pathway in the induction of Pax3 transcription. Furthermore, we establish the function of direct transcriptional repression in the establishment of the Pax3 expression domain. Analysis of a second CNS specific enhancer reveals that Pax3 expression is dependent on autoregulation and Pax7 mediated positive feedback post-neurulation. Together, these data indicate that the temporal activity of two distinct enhancers underlies the regulatory logic of Pax3 expression in the neural tube.
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Villarejo, Balcells Barbara. "Transcriptional regulation of the Alveolar rhabdomysarcoma fusion gene Pax3-Fox01." Thesis, University of London, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528120.
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Blake, Judith A. "The characterisation of Pax3 expressant cells in adult peripheral nerve." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2011. https://ro.ecu.edu.au/theses/448.
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Pax3 has numerous integral functions in embryonic tissue morphogenesis while knowledge of its complex function in cells of adult tissue continues to unfold. Across a variety of adult tissue lineages, the role of Pax3 is principally linked to maintenance of the tissue’s resident stem and progenitor cell population. In adult peripheral nerves, Pax3 is reported to be expressed in nonmyelinating Schwann cells, however, little is known about the purpose of this expression. Based on the evidence of its role in other adult tissue stem and progenitor cell maintenance, it was hypothesised that the cells in adult peripheral nerve that express Pax3 may be Schwann glioblasts. Here, methods have been developed for visualisation of Pax3 expressant cells in normal 60 day old mouse peripheral nerve. Visualisation allowed morphological, anatomical and phenotypic distinctions to be made between these Pax3 expressing cells and Remak bundle nonmyelinating Schwann cells. The distinctions described herein, together with the finding that Pax3 expressing cells co-express stem cell marker Sox2, provides compelling support for the suggestion that a progenitor Schwann cell population may be present in adult mouse peripheral nerve.
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Pasut, Alessandra. "Regulation of Muscle Stem Cell Function by the Transcription Factor Pax7." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32448.
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Pax7 is a paired box transcription factor expressed by all satellite cells which are
critically required for muscle regeneration and growth. The absolute requirements of Pax7 in the maintenance of the satellite cell pool are widely acknowledged. However the mechanisms by which Pax7 executes muscle regeneration or contributes to satellite cell homeostasis remain elusive.
We performed cell and molecular analysis of Pax7 null satellite cells to investigate
muscle stem cell function. Through genome wide studies, we found that genes involved in cell cell interactions, regulation of migration, control of lipid metabolism and inhibition of myogenic differentiation were significantly perturbed in Pax7 null satellite cells. Analysis of satellite cells in vitro showed that Pax7 null satellite cells undergo precocious myogenic differentiation and have perturbed expression of genes involved in the Notch signaling pathway.
We showed that Notch 1 is a novel Pax7 target gene and by using a genetic approach we demonstrated that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) in Pax7 null satellite cells is sufficient to maintain the satellite cell pool as well as to restore their proliferation. Instead of differentiating into myogenic cells and in the absence of a myogenic cue, NICD1 Pax7 null satellite cells become a source of ectopic brown fat within muscles and give rise to brown adipocytes both in vivo and in vitro.
In conclusion we showed that Notch 1 partially rescues Pax7 deficient satellite cells loss and proliferation. Additionally we provide the first evidence that Notch signalling contributes to satellite cell fate by inhibiting terminal myogenic differentiation and inducing brown adipogenesis.
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Feldmann, Jamie Marie. "Analysis of Myogenin Function in Rhabdomyosarcoma Cells." OpenSIUC, 2009. https://opensiuc.lib.siu.edu/theses/7.
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Rhabdomyosarcomas (RMS) are the most common soft tissue cancer among children and are characterized by their expression of the myogenic regulatory factors MyoD and myogenin. Yet RMS cells cannot undergo normal myogenesis and are caught between the proliferation program and the terminal differentiation program. Many questions still remain about the defects present in rhabdomyosarcoma cells. In this work, we set out to understand the role of myogenin in these cells. To begin, we found that myogenin and its co-factors were present in rhabdomyosarcoma cells at levels that should support terminal differentiation. We examined the expression profile of several myogenin target genes in rhabdomyosarcoma cells and then assayed for myogenin activity using luciferase reporter constructs that contain myogenin dependent promoters to test for myogenin function. Many myogenin target genes were down regulated in RMS cells but that the target promoters on the luciferase constructs were activated. Terminal differentiation is a complicated process that involves many proteins. In cancer cells, it is important to compare the levels proteins with known functions to those levels in wild-type cells at the protein and RNA levels. Establishing the defect of rhabdomyosarcoma cells can lead to further insights into normal myogenesis, and may also lead to new therapeutic approaches in the treatment of this childhood cancer.
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Brink, Christopher. "Struktur- und Funktionsanalysen des Pax4-Promotors." [S.l.] : [s.n.], 2001. http://webdoc.sub.gwdg.de/diss/2002/brink/brink.pdf.
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Tyas, David Anthony. "Generation of a Pax6 reporter mouse." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/27562.
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In order to better understand Pax6 function I generated a novel tool – a ‘Pax6 reporter’ transgenic mouse that expresses GFP under the control of Pax6 regulatory elements. The transgenic mouse was generated from a modified yeast artificial chromosome (YAC) that contains the human PAX6 gene and has been previously demonstrated to rescue loss of endogenous Pax6 in Pax6sey/sey mice. The key advantages of a YAC addition transgenic include that it is already known that Pax6 regulatory elements are present over a 200Kb region and inserting a reporter gene into the endogenous Pax6 would not be independent of the endogenous locus. An expression cassette encoding GFP and an IRES-neoR vector were inserted into the YAC in frame with the normal PAX6 translation start point in exon 4, preserving the rest of the PAX6 locus. This put GFP and neomycin under the control of the PAX6 regulatory elements. The modified YAC was then injected into fertilised mouse oocytes to generate nine lines of transgenic mice. Once generated the expression pattern in each line was analysed at a range of developmental stages by imaging appropriate sections of agarose embedded mouse embryos. This confirmed that the expression was the same as the previously reported Pax6 expression pattern. In addition, the copy number and extent of the YAC incorporated in each of the nine lines was investigated.
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Buckle, Adam James. "Regulatory architecture of the Pax6 locus." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/16878.
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Pax6 is a highly conserved developmental regulator with a complex temporal, spatial and quantitative expression pattern, that is crucial for correct development of the central nervous system, the eye, and pancreas. Accordingly, the Pax6 gene resides in a complex genomic locus containing a large array of long-range tissue-specific cis-regulatory elements primarily identified through multispecies sequence conservation and reporter studies. I have set out to understand how the chromatin architecture of the locus contributes to the mechanism and specificity of cis-regulatory interactions. As well as addressing whether the DNA looping model for regulatory interactions applies to the mouse Pax6 locus, I will identify which elements facilitate such interactions and if they vary between cell types. Utilising ChIP-array technology the distribution and variability of key regulatory histone modifications and factors were assessed in a set of Pax6 expressing and non-expressing mouse cell lines, acting as models for different regulatory states of the locus. Work in other loci suggests a key role for CTCF and cohesin (subunit Rad21) in chromatin organisation and long distance regulatory interactions. ChIP-chip for CTCF/Rad21 across the Pax6 locus identified numerous sites within the gene and at distal regulatory locations. The majority of these sites are cell type invariable. The active enhancer modification H3K27ac identified both known and several novel putative enhancer elements distributed through the locus that are highly cell type specific. A subset of CTCF/Rad21 sites also acquire the active enhancer modification H3K27ac in a cell type dependent manor, suggesting that CTCF/Rad21 may facilitate looping to the target gene from these sites. Using reporter based assays, putative regulatory elements marked by the looping factors and active histone modifications showed a diverse range of functional activities. Unexpectedly only 3 of the 7 CTCF sites tested showed classical insulator activity in an enhancer blocking reporter assay. Surprisingly the strongest insulator tested resided within intron 7 the Pax6 gene. Other CTCF/Rad21 sites were neutral or enhancers in the insulator assay. This reveals the disparity between predicting regulatory properties using ChIP binding profiles alone and the actual outcome of functional reporter experiments. A novel element, CTCF6 showed a ChIP signature of CTCF/Rad21/H3K27ac in all Pax6 expressing tissues, and functioned as a strong enhancer in transient transfection and stable LacZ reporter assays. CTCF6 recapitulated a broad range of Pax6 expression patterns, at multiple embryonic stages, including the brain, neural tube and pancreas. A second novel element, E-120 identified in the pancreatic derived cell line, drove stable embryonic reporter expression in the embryonic pancreas and sub set of brain regions. Together this has expanded the repertoire and size of Pax6’s regulatory landscape particular in the upstream region. Chromatin conformation capture (3C) was used to characterise the dynamic chromatin architecture of the locus and identify the interaction profiles from three CTCF/Rad21 binding regulatory locations within the Pax6 locus. This revealed a core set of regulatory interactions with the Pax6 gene, while individual elements showed a more variable set of cell type specific interactions. The CTCF6 enhancer showed highly cell type specific promoter interactions throughout the Pax6 gene, indicative of enhancer-promoter looping not detected in the non-expressing cells. While the downstream site CTCF5 at the edge of a cluster of regulatory elements known as the DRR (differentially regulated region), interacted with both the gene and an upstream element CTCF7 300 kb away only in the Pax6 expressing locus. Together these results reveal Pax6 has a chromatin hub structure with regulatory loops from upstream and downstream bringing distant yet variable active elements in to the vicinity of the Pax6 promoters where they can act. This work has revealed new roles for CTCF/cohesin sites in transcriptional regulation of Pax6 and how the cis-regulatory activity and structure of the locus varies across different cell types.
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Tanimoto, Mimi. "Dissecting auxin signalling : analysis of AXR3/IAA17 expression and interactions in Arabidopsis." Thesis, University of York, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273888.
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Carr, Catherine. "Microarray investigation of the role of Pax6 at the PSPB using a novel tauGFP-Pax6 reporter mouse." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4148.
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Pax6 encodes a highly conserved transcriptional regulator that is widely expressed during development of the eye, olfactory bulbs and central nervous system. Pax6-/- mice exhibit severe brain defects, lack eyes and nasal structures, and die at birth. Included among the functions of Pax6 are cell adhesion, cell cycle progression, axon guidance and boundary formation. The pallial-subpallial boundary (PSPB) is both a physical and gene expression boundary separating dorsal and ventral telencephalon. Pax6 is required for this boundary to develop. In Pax6-/- embryos, genes which normally have a sharp border of expression at the PSPB become ectopically expressed and the radial glial fasicles that make up the physical component of the boundary fail to form. There is also an increase in the number of interneurons migrating dorsally across the boundary to enter the cortex while corticofugal axons struggle to cross the PSPB and enter the ventral telencephalon. Here a novel tauGFP-Pax6 reporter mouse, DTy54, is described in which cells capable of expressing Pax6 are tauGFP positive. In general the expression pattern of tauGFP corresponds well with the known Pax6 expression pattern in the eye and forebrain and the gradient of cortical Pax6 expression from high rostro-laterally to low caudo-medially is also recapitulated by tauGFP. The cytoskeletal localisation of the tauGFP also labels cellular processes and the axons projecting from Pax6 positive cells such as those forming the optic nerve can be clearly seen. At E10.5 the forebrain expression patterns of tauGFP and Pax6 correspond exactly, but at later stages tauGFP expression can be seen in areas negative for Pax6. This can be seen at E12.5 in the ventral telencephalon and in both the dorsal and ventral telencephalon at E15.5. Pax6 and tauGFP expression colocalise more closely in the diencephalon. In situ hybridization analysis of Pax6 and tauGFP transcripts suggests that many of the discrepancies in expression seen at the protein level are due to a longer protein half-life for tauGFP than for Pax6. The expression of tauGFP allows the PSPB to be accurately dissected. The cells from this region can then be sorted by FACS to isolate cells expressing high levels of tauGFP and enrich for the Pax6 positive population. Microarray analysis of gene expression is this population of cells in Pax6+/+.DTy54+ and Pax6sey/sey. DTy54+ embryos is described here. This analysis identified many genes that show a significant change in expression at the PSPB in the absence of Pax6 expression including Ngn2, Lhx6, Neurod6 and CyclinD1 and 2. The biological processes and molecular functions in which these genes are involved were examined to provide insight into the role of Pax6 in this population of cells. Several processes previously reported to be regulated by Pax6 were identified together with a number of novel processes with which Pax6 has not formerly been associated. Some of these include cell cycle, neurogenesis, transcription and metabolic and signalling pathways. This study has also identified many novel downstream targets of Pax6, such as Sema3G and PlexinA4, which will help to elucidate the genetic basis for the Pax6sey/sey phenotype at the PSPB. The changes in expression levels of Ngn2, Lhx6 and Gsh2, identified by microarray, were validated by in situ hybridization, which showed a good correspondence with the microarray results.
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MacMurray, Elizabeth Anne. "Pax5 Signatures: The Identification of Pax5 Isoforms in Developing and Activated B Cell Populations of Rainbow Trout." W&M ScholarWorks, 2012. https://scholarworks.wm.edu/etd/1539626925.
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Grenier, Denis. "De la Pax Romana à la Pax Senensis : Ambrogio Lorenzetti et l'Antiquité." Master's thesis, Université Laval, 1993. http://hdl.handle.net/20.500.11794/17657.
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Faust, Eberhard. "Pax Christi et Pax Caesaris : religionsgeschichtliche, traditionsgeschichtliche und sozialgeschichtliche Studien zum Epheserbrief /." Freiburg : Göttingen : Schweiz : Universitätsverlag ; Vandenhoeck & Ruprecht, 1993. http://catalogue.bnf.fr/ark:/12148/cb355768183.
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Dick, Sarah. "Caspase 3 Cleavage of Pax7 Inhibits Self-Renewal of Satellite Cells." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32233.
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Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, termed satellite cells. Self-renewal and maintenance of the satellite cell niche is coordinated by the transcription factor Pax7, yet continued expression of this protein inhibits the myoblast differentiation program. As such, the reduction or removal of Pax7 may denote a key prerequisite for satellite cells to abandon self-renewal and acquire differentiation competence. Here, we identify caspase 3 cleavage inactivation of Pax7 as a crucial step for terminating the self-renewal process. Inhibition of caspase 3 results in elevated Pax7 protein and satellite cell self-renewal, while caspase activation leads to Pax7 cleavage and initiation of the myogenic differentiation program. We have also noted that casein kinase 2 (CK2) directed phosphorylation of Pax7 attenuates caspase directed cleavage. Together, these results demonstrate that satellite cell fate is dependent on opposing post-translational modifications of the Pax7 protein.
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Jackson, Anna Francina. "The Functional Characterization of Wdr68 Regulation of Pax7 Activity in Myogenesis." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28879.
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In response to tissue trauma, quiescent satellite cells in adult skeletal muscle undergo proliferative activation and migrate to the site of injury where they differentiate and fuse to mend and replace damaged myofibers. The tightly synchronized expression of myogenic regulatory factors plays a critical role in orchestrating the regenerative process. In recent studies, we identified the transcription factor Pax7 as able to recruit the Wdr5-Ash2L-MLL2 histone methyltransferase complex to the -57.5kb Myf5 enhancer and to activate Myf5 transcription. We also identified Wdr68 as a putative Pax7 binding protein. Wdr68 is a scaffold protein thought to integrate Shh signaling but about which very little is known. Therefore, we set out to characterize a role for Wdr68 with Pax7 in early myogenesis. The interaction of endogenous Pax7 and exogenous Wdr68 was validated by reciprocal co-immunoprecipitation and western blot analysis. Manipulation of Wdr68 levels in primary myoblasts followed by real-time PCR analysis of Pax7 target genes suggests that Wdr68 acts as a negative regulator of Pax7. It has been determined by ChIP experiments that Wdr68 does not bind chromatin at some known genomic Pax7 binding sites. In addition, Wdr68 appears not to function by regulating Pax7 nuclear localization. These experiments provide new insights into the molecular control of Pax7 function during regenerative myogenesis and emphasize its complexity.
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Roeb, Wendy Linette. "The role of PAX3-FOXO1 in the pathogenesis of alveolar rhabdomyosarcoma." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3274591.
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Thesis (Ph. D.)--University of California, San Diego, 2007.Title from first page of PDF file (viewed June 2, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.