To see the other types of publications on this topic, follow the link: Axon development.
Journal articles on the topic 'Axon development'
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 'Axon development.'
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
Peckol, E. L., J. A. Zallen, J. C. Yarrow, and C. I. Bargmann. "Sensory activity affects sensory axon development in C. elegans." Development 126, no. 9 (May 1, 1999): 1891–902. http://dx.doi.org/10.1242/dev.126.9.1891.
Full textAbstract:
The simple nervous system of the nematode C. elegans consists of 302 neurons with highly reproducible morphologies, suggesting a hard-wired program of axon guidance. Surprisingly, we show here that sensory activity shapes sensory axon morphology in C. elegans. A class of mutants with deformed sensory cilia at their dendrite endings have extra axon branches, suggesting that sensory deprivation disrupts axon outgrowth. Mutations that alter calcium channels or membrane potential cause similar defects. Cell-specific perturbations of sensory activity can cause cell-autonomous changes in axon morphology. Although the sensory axons initially reach their targets in the embryo, the mutations that alter sensory activity cause extra axon growth late in development. Thus, perturbations of activity affect the maintenance of sensory axon morphology after an initial pattern of innervation is established. This system provides a genetically tractable model for identifying molecular mechanisms linking neuronal activity to nervous system structure.
2
Whitington, P. M. "The early development of motor axon pathways in the the establishment of the segmental nerves in the." Development 105, no. 4 (April 1, 1989): 715–21. http://dx.doi.org/10.1242/dev.105.4.715.
Full textAbstract:
This study has identified the first five motor neurones axons out of the segmental nerves in the thoracic and has traced the pathways followed by these axons up divergence into the ganglionic nerve roots. These out axons in a stereotyped sequence over a short to 2% of embryonic development. Motor axons initially contact the dorsal basal lamina and then parallel array just beneath this membrane. At the edge axons diverge into either of two pathways: an anterior corresponding to nerve root 3 which is pioneered by axon to leave the CNS; and a posterior pathway, root 5, which is pioneered by the second motor axon. axon appears to grow circumferentially around the between the body wall and the base of the coxa, while closely associated with the filopodia or axons of the peripheral pioneer neurones. The later motor axons pathways pioneered by these first two axons. A small molecular markers would be sufficient to generate the of axon growth by these early motor neurones and some cues may be used to guide afferent axons into the CNS.
3
Johnson, J. Kelly, and V. A. Casagrande. "Prenatal development of axon outgrowth and connectivity in the ferret visual system." Visual Neuroscience 10, no. 1 (January 1993): 117–30. http://dx.doi.org/10.1017/s0952523800003266.
Full textAbstract:
AbstractThe objective of this study was to determine when the retina, lateral geniculate nucleus (LGN), and striate cortex first send out axons, and first connect with each other, during embryonic development in the ferret. Specifically, we were interested in the timing relationship between axon outgrowth and known temporal patterns of neurogenesis in the LGN and striate cortex. Ferrets (Mustela putorius furo) were selected for study because of their immature developmental state in late gestation and relatively large litters.We examined axon outgrowth from the retina, and anlagen of presumptive LGN and striate cortex between embryonic day 21–30 (E21–E30) using in situ inoculations of two fluorescent lipophilic dyes, Dil and DiA. Dil inoculations were made into the cortex and contralateral thalamus, and DiA inoculations were made into the contralateral eye. Retinal axon termination zones in the diencephalon following the DiA inoculations were used to validate the location of the LGN.Visual cortex and LGN neurogenesis begins at E20 in ferrets. No axon outgrowth could be documented from retina or anlagen of striate cortex and LGN until E24. At E24 some retinal axons reach and cross the chiasm, cortical axons extend some distance within the cortical radiations, and thalamic axons are within the internal capsule. Retinogeniculate, geniculocortical, and corticogeniculate axons extend to their target structures by E27, as evidenced by retrograde labeling in cells of origin.These data suggest that in the ferret retina, and developing LGN and striate cortex, (1) axon outgrowth from each visual area begins within 24-h of each other, after neurogenesis has begun at the source but before it is complete in the target; (2) axons may be generated before parent cell bodies have completed migration; and (3) arriving axons are in a position to influence target structures almost from their inception.
4
Goslin, K., and G. Banker. "Experimental observations on the development of polarity by hippocampal neurons in culture." Journal of Cell Biology 108, no. 4 (April 1, 1989): 1507–16. http://dx.doi.org/10.1083/jcb.108.4.1507.
Full textAbstract:
In culture, hippocampal neurons develop a polarized form, with a single axon and several dendrites. Transecting the axons of hippocampal neurons early in development can cause an alteration of polarity; a process that would have become a dendrite instead becomes the axon (Dotti, C. G., and G. A. Banker. 1987. Nature (Lond.). 330:254-256). To investigate this phenomenon more systematically, we transected axons at varying lengths. The greater the distance of the transection from the soma, the greater the probability for regrowth of the original axon. However, it was not the absolute length of the axonal stump that determined the response to transection, but rather its length relative to the lengths of the cell's other processes. If one process was greater than 10 microns longer than the others, it invariably became the axon regardless of its identity before transection. Conversely, when a cell's processes were nearly equal in length, it was impossible to predict which would become the axon. In these cases, axonal outgrowth began only after a long latency. During this interval, the processes appeared to be in dynamic equilibrium, some growing for short distances while others retracted. When one process exceeded the others by a critical length, it rapidly elongated to become the axon. The establishment of neuronal polarity during normal development may similarly involve an interaction among processes whose identities have not yet been determined. When, by chance, one exceeds the others by a critical length, it becomes specified as the axon.
5
Nishikimi, Mitsuaki, Koji Oishi, and Kazunori Nakajima. "Axon Guidance Mechanisms for Establishment of Callosal Connections." Neural Plasticity 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/149060.
Full textAbstract:
Numerous studies have investigated the formation of interhemispheric connections which are involved in high-ordered functions of the cerebral cortex in eutherian animals, including humans. The development of callosal axons, which transfer and integrate information between the right/left hemispheres and represent the most prominent commissural system, must be strictly regulated. From the beginning of their growth, until reaching their targets in the contralateral cortex, the callosal axons are guided mainly by two environmental cues: (1) the midline structures and (2) neighboring? axons. Recent studies have shown the importance of axona guidance by such cues and the underlying molecular mechanisms. In this paper, we review these guidance mechanisms during the development of the callosal neurons. Midline populations express and secrete guidance molecules, and “pioneer” axons as well as interactions between the medial and lateral axons are also involved in the axon pathfinding of the callosal neurons. Finally, we describe callosal dysgenesis in humans and mice, that results from a disruption of these navigational mechanisms.
6
Llobet Rosell, Arnau, and Lukas J. Neukomm. "Axon death signalling in Wallerian degeneration among species and in disease." Open Biology 9, no. 8 (August 2019): 190118. http://dx.doi.org/10.1098/rsob.190118.
Full textAbstract:
Axon loss is a shared feature of nervous systems being challenged in neurological disease, by chemotherapy or mechanical force. Axons take up the vast majority of the neuronal volume, thus numerous axonal intrinsic and glial extrinsic support mechanisms have evolved to promote lifelong axonal survival. Impaired support leads to axon degeneration, yet underlying intrinsic signalling cascades actively promoting the disassembly of axons remain poorly understood in any context, making the development to attenuate axon degeneration challenging. Wallerian degeneration serves as a simple model to study how axons undergo injury-induced axon degeneration (axon death). Severed axons actively execute their own destruction through an evolutionarily conserved axon death signalling cascade. This pathway is also activated in the absence of injury in diseased and challenged nervous systems. Gaining insights into mechanisms underlying axon death signalling could therefore help to define targets to block axon loss. Herein, we summarize features of axon death at the molecular and subcellular level. Recently identified and characterized mediators of axon death signalling are comprehensively discussed in detail, and commonalities and differences across species highlighted. We conclude with a summary of engaged axon death signalling in humans and animal models of neurological conditions. Thus, gaining mechanistic insights into axon death signalling broadens our understanding beyond a simple injury model. It harbours the potential to define targets for therapeutic intervention in a broad range of human axonopathies.
7
Zallen, J. A., S. A. Kirch, and C. I. Bargmann. "Genes required for axon pathfinding and extension in the C. elegans nerve ring." Development 126, no. 16 (August 15, 1999): 3679–92. http://dx.doi.org/10.1242/dev.126.16.3679.
Full textAbstract:
Over half of the neurons in Caenorhabditis elegans send axons to the nerve ring, a large neuropil in the head of the animal. Genetic screens in animals that express the green fluorescent protein in a subset of sensory neurons identified eight new sax genes that affect the morphology of nerve ring axons. sax-3/robo mutations disrupt axon guidance in the nerve ring, while sax-5, sax-9 and unc-44 disrupt both axon guidance and axon extension. Axon extension and guidance proceed normally in sax-1, sax-2, sax-6, sax-7 and sax-8 mutants, but these animals exhibit later defects in the maintenance of nerve ring structure. The functions of existing guidance genes in nerve ring development were also examined, revealing that SAX-3/Robo acts in parallel to the VAB-1/Eph receptor and the UNC-6/netrin, UNC-40/DCC guidance systems for ventral guidance of axons in the amphid commissure, a major route of axon entry into the nerve ring. In addition, SAX-3/Robo and the VAB-1/Eph receptor both function to prevent aberrant axon crossing at the ventral midline. Together, these genes define pathways required for axon growth, guidance and maintenance during nervous system development.
8
Birgbauer, Eric, Stephen F. Oster, Christophe G. Severin, and David W. Sretavan. "Retinal axon growth cones respond to EphB extracellular domains as inhibitory axon guidance cues." Development 128, no. 15 (August 1, 2001): 3041–48. http://dx.doi.org/10.1242/dev.128.15.3041.
Full textAbstract:
Axon pathfinding relies on cellular signaling mediated by growth cone receptor proteins responding to ligands, or guidance cues, in the environment. Eph proteins are a family of receptor tyrosine kinases that govern axon pathway development, including retinal axon projections to CNS targets. Recent examination of EphB mutant mice, however, has shown that axon pathfinding within the retina to the optic disc is dependent on EphB receptors, but independent of their kinase activity. Here we show a function for EphB1, B2 and B3 receptor extracellular domains (ECDs) in inhibiting mouse retinal axons when presented either as substratum-bound proteins or as soluble proteins directly applied to growth cones via micropipettes. In substratum choice assays, retinal axons tended to avoid EphB-ECDs, while time-lapse microscopy showed that exposure to soluble EphB-ECD led to growth cone collapse or other inhibitory responses. These results demonstrate that, in addition to the conventional role of Eph proteins signaling as receptors, EphB receptor ECDs can also function in the opposite role as guidance cues to alter axon behavior. Furthermore, the data support a model in which dorsal retinal ganglion cell axons heading to the optic disc encounter a gradient of inhibitory EphB proteins which helps maintain tight axon fasciculation and prevents aberrant axon growth into ventral retina. In conclusion, development of neuronal connectivity may involve the combined activity of Eph proteins serving as guidance receptors and as axon guidance cues.
9
Whitlock, K. E. "Development of Drosophila wing sensory neurons in mutants with missing or modified cell surface molecules." Development 117, no. 4 (April 1, 1993): 1251–60. http://dx.doi.org/10.1242/dev.117.4.1251.
Full textAbstract:
The neurons of the sensory receptors on the wing of Drosophila melanogaster have highly characteristic axon projections in the central nervous system (CNS). The morphology of these projections was studied in flies bearing mutations that affect cell surface molecules thought to be important in axon guidance. The animals used were mutant for the fasciclinI (fasI), fasciclinII (fasII), fasciclinIII (fasIII) and neurally altered carbohydrate (nac) genes. Axon populations were visualized by staining with DiI and light-reacting the dye with diaminobenzidine to yield permanent preparations. The fasI, fasII and fasIII mutants as well as the nac mutant display altered axonal trajectories in the CNS. One phenotype seen in fasII mutants and in animals mutant for both fasI and fasIII was extra branching within the axon projection pattern. A second phenotype observed was a reduction or complete loss of one of the tracts, apparently due to the axons shifting to a neighboring tract. This was seen in the most extreme form in nac mutants and to a lesser degree in fasIII mutants. To determine if the mutations discussed here affected axon guidance, wing discs were analyzed using the antibody 22C10 to label sensory neurons in the wing during metamorphosis. Both misrouting of axons and the appearance of ectopic neurons in the wing were observed. In the fasI:fasIII, the fasII and the nac mutants, there was misrouting of sensory axons in the developing wing. In addition, the fasII and nac mutants displayed ectopic sensory neurons in the wing. This implies that the cell surface molecules missing (fasciclins) or modified (by the nac gene product), in these mutants may play a role in both neurogenesis and axon guidance.
10
Hao, Hailing, and David I. Shreiber. "Axon Kinematics Change During Growth and Development." Journal of Biomechanical Engineering 129, no. 4 (February 14, 2007): 511–22. http://dx.doi.org/10.1115/1.2746372.
Full textAbstract:
The microkinematic response of axons to mechanical stretch was examined in the developing chick embryo spinal cord during a period of rapid growth and myelination. Spinal cords were isolated at different days of embryonic (E) development post-fertilization (E12, E14, E16, and E18) and stretched 0%, 5%, 10%, 15%, and 20%, respectively. During this period, the spinal cord grew ∼55% in length, and white matter tracts were myelinated significantly. The spinal cords were fixed with paraformaldehyde at the stretched length, sectioned, stained immunohistochemically for neurofilament proteins, and imaged with epifluorescence microscopy. Axons in unstretched spinal cords were undulated, or tortuous, to varying degrees, and appeared to straighten with stretch. The degree of tortuosity (ratio of the segment’s pathlength to its end-to-end length) was quantified in each spinal cord by tracing several hundred randomly selected axons. The change in tortuosity distributions with stretch indicated that axons switched from non-affine, uncoupled behavior at low stretch levels to affine, coupled behavior at high stretch levels, which was consistent with previous reports of axon behavior in the adult guinea pig optic nerve (Bain, Shreiber, and Meaney, J. Biomech. Eng., 125(6), pp. 798–804). A mathematical model previously proposed by Bain et al. was applied to quantify the transition in kinematic behavior. The results indicated that significant percentages of axons demonstrated purely non-affine behavior at each stage, but that this percentage decreased from 64% at E12 to 30% at E18. The decrease correlated negatively to increases in both length and myelination with development, but the change in axon kinematics could not be explained by stretch applied during physical growth of the spinal cord. The relationship between tissue-level and axonal-level deformation changes with development, which can have important implications in the response to physiological forces experienced during growth and trauma.
11
Sherry, Tessa, Ava Handley, Hannah R. Nicholas, and Roger Pocock. "Harmonization of L1CAM expression facilitates axon outgrowth and guidance of a motor neuron." Development 147, no. 20 (September 29, 2020): dev193805. http://dx.doi.org/10.1242/dev.193805.
Full textAbstract:
ABSTRACTBrain development requires precise regulation of axon outgrowth, guidance and termination by multiple signaling and adhesion molecules. How the expression of these neurodevelopmental regulators is transcriptionally controlled is poorly understood. The Caenorhabditis elegans SMD motor neurons terminate axon outgrowth upon sexual maturity and partially retract their axons during early adulthood. Here we show that C-terminal binding protein 1 (CTBP-1), a transcriptional corepressor, is required for correct SMD axonal development. Loss of CTBP-1 causes multiple defects in SMD axon development: premature outgrowth, defective guidance, delayed termination and absence of retraction. CTBP-1 controls SMD axon guidance by repressing the expression of SAX-7, an L1 cell adhesion molecule (L1CAM). CTBP-1-regulated repression is crucial because deregulated SAX-7/L1CAM causes severely aberrant SMD axons. We found that axonal defects caused by deregulated SAX-7/L1CAM are dependent on a distinct L1CAM, called LAD-2, which itself plays a parallel role in SMD axon guidance. Our results reveal that harmonization of L1CAM expression controls the development and maturation of a single neuron.
12
Liu, Zhi-Zhi, Jian Zhu, Chang-Ling Wang, Xin Wang, Ying-Ying Han, Ling-Yan Liu, and Hong A. Xu. "CRMP2 and CRMP4 Are Differentially Required for Axon Guidance and Growth in Zebrafish Retinal Neurons." Neural Plasticity 2018 (June 21, 2018): 1–9. http://dx.doi.org/10.1155/2018/8791304.
Full textAbstract:
Axons are directed to their correct targets by guidance cues during neurodevelopment. Many axon guidance cues have been discovered; however, much less known is about how the growth cones transduce the extracellular guidance cues to intracellular responses. Collapsin response mediator proteins (CRMPs) are a family of intracellular proteins that have been found to mediate growth cone behavior in vitro; however, their roles in vivo in axon development are much less explored. In zebrafish embryos, we find that CRMP2 and CRMP4 are expressed in the retinal ganglion cell layer when retinal axons are crossing the midline. Knocking down CRMP2 causes reduced elongation and premature termination of the retinal axons, while knocking down CRMP4 results in ipsilateral misprojections of retinal axons that would normally project to the contralateral brain. Furthermore, CRMP4 synchronizes with neuropilin 1 in retinal axon guidance, suggesting that CRMP4 might mediate the semaphorin/neuropilin signaling pathway. These results demonstrate that CRMP2 and CRMP4 function differentially in axon development in vivo.
13
Sun, Tao, Nuo Yu, Lu-Kai Zhai, Na Li, Chao Zhang, Liang Zhou, Zhuo Huang, Xing-Yu Jiang, Ying Shen, and Zhe-Yu Chen. "c-Jun NH2-terminal Kinase (JNK)-interacting Protein-3 (JIP3) Regulates Neuronal Axon Elongation in a Kinesin- and JNK-dependent Manner." Journal of Biological Chemistry 288, no. 20 (April 10, 2013): 14531–43. http://dx.doi.org/10.1074/jbc.m113.464453.
Full textAbstract:
The development of neuronal polarity is essential for the establishment of the accurate patterning of neuronal circuits in the brain. However, little is known about the underlying molecular mechanisms that control rapid axon elongation during neuronal development. Here, we report that c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) is highly expressed at axon tips during the critical period for axon development. Using gain- and loss-of-function approaches, immunofluorescence analysis, and in utero electroporation, we find that JIP3 can enhance axon elongation in primary hippocampal neurons and cortical neurons in vivo. We further demonstrate that JIP3 promotes axon elongation in a kinesin- and JNK-dependent manner using several deletion mutants of JIP3. Next, we demonstrate that the successful transportation of JIP3 to axon tips by kinesin is a prerequisite for enhancing JNK phosphorylation in this area and therefore promotes axon elongation, constituting a novel mechanism for coupling JIP3 anterograde transport with JNK signaling at the distal axons and axon elongation. Finally, our immunofluorescence data suggest that the activation of JNK at axon tips facilitates axon elongation by modulating cofilin activity and actin filament dynamics. These findings may have important implications for our understanding of neuronal axon elongation during development.
14
Florence, S. L., and V. A. Casagrande. "Development of geniculocortical axon arbors in a primate." Visual Neuroscience 5, no. 3 (September 1990): 291–309. http://dx.doi.org/10.1017/s0952523800000365.
Full textAbstract:
AbstractThe main objective of the present study was to describe the postnatal development of magnocellular and parvocellular LGN axons within the primate striate cortex. For this purpose, we bulk labeled axons in neonatal prosimians (galagos) in vivo or in vitro at regular intervals from birth (PO) to 12 weeks after birth by injecting horseradish peroxidase (HRP) into white matter anterior to the striate cortex. Filled axons within layer IV were reconstructed, quantitatively analyzed, and compared to a population of adult axons described previously (Florence & Casagrande, 1987).Our results show that although axons are morphologically immature at birth, they are restricted to the upper (IVα) and lower (IVβ) tiers of layer IV of the striate cortex as in adults. In adults, we referred to the presumed magnocellular LGN axons terminating in IVα as type I and the presumed parvocellular axons terminating in IVβ as type II. We used the same convention for developing axons.From birth to 3 weeks postnatal, type I and II axon classes are more variable in appearance than adult counterparts, and are not morphologically class distinct. As axons mature, parent axon shafts increase in caliber, arbors become smaller and more radial, and other immature features (e.g. spikes, protrusions, growth cones) are less evident. Both arbor classes mature slowly and some still exhibit immature features (e.g. growth cones) as late as 12 weeks postnatally. Although arbors do not show class-distinctive features until late in development, each class does show some unique maturational trends. Type I arbors are only slightly larger than adult counterparts at birth, whereas type II arbors are dramatically larger. Type I arbors increase in branch complexity with age, whereas type II arbors simply show a shift in complexity toward the center of the arbor with decreasing size over time. These growth trends suggest that magnocellular and parvocellular pathways to cortex could be differentially vulnerable to the manipulation of postnatal visual experience.
15
Rowan, Alison. "Axon development branches out." Nature Reviews Neuroscience 6, no. 10 (October 2005): 751. http://dx.doi.org/10.1038/nrn1777.
Full text
16
Onishi, Keisuke, Runyi Tian, Bo Feng, Yiqiong Liu, Junkai Wang, Yinan Li, and Yimin Zou. "LRRK2 mediates axon development by regulating Frizzled3 phosphorylation and growth cone–growth cone communication." Proceedings of the National Academy of Sciences 117, no. 30 (July 8, 2020): 18037–48. http://dx.doi.org/10.1073/pnas.1921878117.
Full textAbstract:
Axon–axon interactions are essential for axon guidance during nervous system wiring. However, it is unknown whether and how the growth cones communicate with each other while sensing and responding to guidance cues. We found that the Parkinson’s disease gene, leucine-rich repeat kinase 2 (LRRK2), has an unexpected role in growth cone–growth cone communication. The LRRK2 protein acts as a scaffold and induces Frizzled3 hyperphosphorylation indirectly by recruiting other kinases and also directly phosphorylates Frizzled3 on threonine 598 (T598). InLRRK1orLRRK2single knockout,LRRK1/2double knockout, andLRRK2 G2019Sknockin, the postcrossing spinal cord commissural axons are disorganized and showed anterior–posterior guidance errors after midline crossing. Growth cones from eitherLRRK2knockout orG2019Sknockin mice showed altered interactions, suggesting impaired communication. Intercellular interaction between Frizzled3 and Vangl2 is essential for planar cell polarity signaling. We show here that this interaction is regulated by phosphorylation of Frizzled3 at T598 and can be regulated by LRRK2 in a kinase activity-dependent way. In theLRRK1/2double knockout orLRRK2 G2019Sknockin, the dopaminergic axon bundle in the midbrain was significantly widened and appeared disorganized, showing aberrant posterior-directed growth. Our findings demonstrate that LRRK2 regulates growth cone–growth cone communication in axon guidance and that both loss-of-function mutation and a gain-of-function mutation (G2019S)cause axon guidance defects in development.
17
Biswas, Sayantanee, Michelle R. Emond, Phan Q. Duy, Le T. Hao, Christine E. Beattie, and James D. Jontes. "Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish." Molecular Biology of the Cell 25, no. 5 (March 2014): 633–42. http://dx.doi.org/10.1091/mbc.e13-08-0475.
Full textAbstract:
The proper assembly of neural circuits during development requires the precise control of axon outgrowth, guidance, and arborization. Although the protocadherin family of cell surface receptors is widely hypothesized to participate in neural circuit assembly, their specific roles in neuronal development remain largely unknown. Here we demonstrate that zebrafish pcdh18b is involved in regulating axon arborization in primary motoneurons. Although axon outgrowth and elongation appear normal, antisense morpholino knockdown of pcdh18b results in dose-dependent axon branching defects in caudal primary motoneurons. Cell transplantation experiments show that this effect is cell autonomous. Pcdh18b interacts with Nap1, a core component of the WAVE complex, through its intracellular domain, suggesting a role in the control of actin assembly. Like that of Pcdh18b, depletion of Nap1 results in reduced branching of motor axons. Time-lapse imaging and quantitative analysis of axon dynamics indicate that both Pcdh18b and Nap1 regulate axon arborization by affecting the density of filopodia along the shaft of the extending axon.
18
Ware, Michelle, Colin P. Waring, and Frank R. Schubert. "Development of the Early Axon Scaffold in the Rostral Brain of the Small Spotted Cat Shark (Scyliorhinus canicula) Embryo." International Scholarly Research Notices 2014 (October 29, 2014): 1–8. http://dx.doi.org/10.1155/2014/196594.
Full textAbstract:
The cat shark is increasingly used as a model for Chondrichthyes, an evolutionarily important sister group of the bony vertebrates that include teleosts and tetrapods. In the bony vertebrates, the first axon tracts form a highly conserved early axon scaffold. The corresponding structure has not been well characterised in cat shark and will prove a useful model for comparative studies. Using pan-neural markers, the early axon scaffold of the cat shark, Scyliorhinus canicula, was analysed. Like in other vertebrates, the medial longitudinal fascicle was the first axon tract to form from a small cluster of neurones in the ventral brain. Subsequently, additional neuronal clusters and axon tracts emerged which formed an array of longitudinal, transversal, and commissural axons tracts in the Scyliorhinus canicula embryonic brain. The first structures to appear after the medial longitudinal fascicle were the tract of the postoptic commissure, the dorsoventral diencephalic tract, and the descending tract of the mesencephalic nucleus of the trigeminal nerve. These results confirm that the early axon scaffold in the embryonic brain is highly conserved through vertebrate evolution.
19
Kim, Sung Wook, and Kyong-Tai Kim. "Expression of Genes Involved in Axon Guidance: How Much Have We Learned?" International Journal of Molecular Sciences 21, no. 10 (May 18, 2020): 3566. http://dx.doi.org/10.3390/ijms21103566.
Full textAbstract:
Neuronal axons are guided to their target during the development of the brain. Axon guidance allows the formation of intricate neural circuits that control the function of the brain, and thus the behavior. As the axons travel in the brain to find their target, they encounter various axon guidance cues, which interact with the receptors on the tip of the growth cone to permit growth along different signaling pathways. Although many scientists have performed numerous studies on axon guidance signaling pathways, we still have an incomplete understanding of the axon guidance system. Lately, studies on axon guidance have shifted from studying the signal transduction pathways to studying other molecular features of axon guidance, such as the gene expression. These new studies present evidence for different molecular features that broaden our understanding of axon guidance. Hence, in this review we will introduce recent studies that illustrate different molecular features of axon guidance. In particular, we will review literature that demonstrates how axon guidance cues and receptors regulate local translation of axonal genes and how the expression of guidance cues and receptors are regulated both transcriptionally and post-transcriptionally. Moreover, we will highlight the pathological relevance of axon guidance molecules to specific diseases.
20
Bruce, Freyja M., Samantha Brown, Jonathan N. Smith, Peter G. Fuerst, and Lynda Erskine. "DSCAM promotes axon fasciculation and growth in the developing optic pathway." Proceedings of the National Academy of Sciences 114, no. 7 (January 30, 2017): 1702–7. http://dx.doi.org/10.1073/pnas.1618606114.
Full textAbstract:
Although many aspects of optic pathway development are beginning to be understood, the mechanisms promoting the growth of retinal ganglion cell (RGC) axons toward visual targets remain largely unknown. Down syndrome cell adhesion molecule (Dscam) is expressed by mouse RGCs shortly after they differentiate at embryonic day 12 and is essential for multiple aspects of postnatal visual system development. Here we show that Dscam is also required during embryonic development for the fasciculation and growth of RGC axons. Dscam is expressed along the developing optic pathway in a pattern consistent with a role in regulating RGC axon outgrowth. In mice carrying spontaneous mutations in Dscam (Dscamdel17; Dscam2J), RGC axons pathfind normally, but growth from the chiasm toward their targets is impaired, resulting in a delay in RGC axons reaching the dorsal thalamus compared with that seen in wild-type littermates. Conversely, Dscam gain of function results in exuberant growth into the dorsal thalamus. The growth of ipsilaterally projecting axons is particularly affected. Axon organization in the optic chiasm and tract and RGC growth cone morphologies are also altered in Dscam mutants. In vitro DSCAM promotes RGC axon growth and fasciculation, and can act independently of cell contact. In vitro and in situ DSCAM is required both in the RGC axons and in their environment for the promotion of axon outgrowth, consistent with a homotypic mode of action. These findings identify DSCAM as a permissive signal that promotes the growth and fasciculation of RGC axons, controlling the timing of when RGC axons reach their targets.
21
Debanne, Dominique, Emilie Campanac, Andrzej Bialowas, Edmond Carlier, and Gisèle Alcaraz. "Axon Physiology." Physiological Reviews 91, no. 2 (April 2011): 555–602. http://dx.doi.org/10.1152/physrev.00048.2009.
Full textAbstract:
Axons are generally considered as reliable transmission cables in which stable propagation occurs once an action potential is generated. Axon dysfunction occupies a central position in many inherited and acquired neurological disorders that affect both peripheral and central neurons. Recent findings suggest that the functional and computational repertoire of the axon is much richer than traditionally thought. Beyond classical axonal propagation, intrinsic voltage-gated ionic currents together with the geometrical properties of the axon determine several complex operations that not only control signal processing in brain circuits but also neuronal timing and synaptic efficacy. Recent evidence for the implication of these forms of axonal computation in the short-term dynamics of neuronal communication is discussed. Finally, we review how neuronal activity regulates both axon morphology and axonal function on a long-term time scale during development and adulthood.
22
Udvadia, A. J., R. W. Koster, and J. H. Skene. "GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals for axon growth during CNS development and regeneration." Development 128, no. 7 (April 1, 2001): 1175–82. http://dx.doi.org/10.1242/dev.128.7.1175.
Full textAbstract:
A pivotal event in neural development is the point at which differentiating neurons become competent to extend long axons. Initiation of axon growth is equally critical for regeneration. Yet we have a limited understanding of the signaling pathways that regulate the capacity for axon growth during either development or regeneration. Expression of a number of genes encoding growth associated proteins (GAPs) accompanies both developmental and regenerative axon growth and has led to the suggestion that the same signaling pathways regulate both modes of axon growth. We have tested this possibility by asking whether a promoter fragment from a well characterized GAP gene, GAP-43, is sufficient to activate expression in both developing and regenerating neurons. We generated stable lines of transgenic zebrafish that express green fluorescent protein (GFP) under regulation of a 1 kb fragment of the rat GAP-43 gene, a fragment that contains a number of evolutionarily conserved elements. Analysis of GFP expression in these lines confirms that the rat 1 kb region can direct growth-associated expression of the transgene in differentiating neurons that extend long axons. Furthermore, this region supports developmental down-regulation of transgene expression which, like the endogenous gene, coincides with neuronal maturation. Strikingly, these same sequences are insufficient for directing expression in regenerating neurons. This finding suggests that signaling pathways regulating axon growth during development and regeneration are not the same. While these results do not exclude the possibility that pathways involved in developmental axon growth are also active in regenerative growth, they do indicate that signaling pathway(s) controlling activation of the GAP-43 gene after CNS injury differ in at least one key component from the signals controlling essential features of developmental axon growth.
23
Beattie, C. E., E. Melancon, and J. S. Eisen. "Mutations in the stumpy gene reveal intermediate targets for zebrafish motor axons." Development 127, no. 12 (June 15, 2000): 2653–62. http://dx.doi.org/10.1242/dev.127.12.2653.
Full textAbstract:
Primary motoneurons, the earliest developing spinal motoneurons in zebrafish, have highly stereotyped axon projections. Although much is known about the development of these neurons, the molecular cues guiding their axons have not been identified. In a screen designed to reveal mutations affecting motor axons, we isolated two mutations in the stumpy gene that dramatically affect pathfinding by the primary motoneuron, CaP. In stumpy mutants, CaP axons extend along the common pathway, a region shared by other primary motor axons, but stall at an intermediate target, the horizontal myoseptum, and fail to extend along their axon-specific pathway during the first day of development. Later, most CaP axons progress a short distance beyond the horizontal myoseptum, but tend to stall at another intermediate target. Mosaic analysis revealed that stumpy function is needed both autonomously in CaP and non-autonomously in other cells. stumpy function is also required for axons of other primary and secondary motoneurons to progress properly past intermediate targets and to branch. These results reveal a series of intermediate targets involved in motor axon guidance and suggest that stumpy function is required for motor axons to progress from proximally located intermediate targets to distally located ones.
24
Kawano, Yoji, Takeshi Yoshimura, Daisuke Tsuboi, Saeko Kawabata, Takako Kaneko-Kawano, Hiromichi Shirataki, Tadaomi Takenawa, and Kozo Kaibuchi. "CRMP-2 Is Involved in Kinesin-1-Dependent Transport of the Sra-1/WAVE1 Complex and Axon Formation." Molecular and Cellular Biology 25, no. 22 (November 15, 2005): 9920–35. http://dx.doi.org/10.1128/mcb.25.22.9920-9935.2005.
Full textAbstract:
ABSTRACT A neuron has two types of highly polarized cell processes, the single axon and multiple dendrites. One of the fundamental questions of neurobiology is how neurons acquire such specific and polarized morphologies. During neuronal development, various actin-binding proteins regulate dynamics of actin cytoskeleton in the growth cones of developing axons. The regulation of actin cytoskeleton in the growth cones is thought to be involved in axon outgrowth and axon-dendrite specification. However, it is largely unknown which actin-binding proteins are involved in axon-dendrite specification and how they are transported into the developing axons. We have previously reported that collapsin response mediator protein 2 (CRMP-2) plays a critical role in axon outgrowth and axon-dendrite specification (N. Inagaki, K. Chihara, N. Arimura, C. Menager, Y. Kawano, N. Matsuo, T. Nishimura, M. Amano, and K. Kaibuchi, Nat. Neurosci. 4:781-782, 2001). Here, we found that CRMP-2 interacted with the specifically Rac1-associated protein 1 (Sra-1)/WASP family verprolin-homologous protein 1 (WAVE1) complex, which is a regulator of actin cytoskeleton. The knockdown of Sra-1 and WAVE1 by RNA interference canceled CRMP-2-induced axon outgrowth and multiple-axon formation in cultured hippocampal neurons. We also found that CRMP-2 interacted with the light chain of kinesin-1 and linked kinesin-1 to the Sra-1/WAVE1 complex. The knockdown of CRMP-2 and kinesin-1 delocalized Sra-1 and WAVE1 from the growth cones of axons. These results suggest that CRMP-2 transports the Sra-1/WAVE1 complex to axons in a kinesin-1-dependent manner and thereby regulates axon outgrowth and formation.
25
Padmanabhan, Pranesh, and Geoffrey J. Goodhill. "Axon growth regulation by a bistable molecular switch." Proceedings of the Royal Society B: Biological Sciences 285, no. 1877 (April 18, 2018): 20172618. http://dx.doi.org/10.1098/rspb.2017.2618.
Full textAbstract:
For the brain to function properly, its neurons must make the right connections during neural development. A key aspect of this process is the tight regulation of axon growth as axons navigate towards their targets. Neuronal growth cones at the tips of developing axons switch between growth and paused states during axonal pathfinding, and this switching behaviour determines the heterogeneous axon growth rates observed during brain development. The mechanisms controlling this switching behaviour, however, remain largely unknown. Here, using mathematical modelling, we predict that the molecular interaction network involved in axon growth can exhibit bistability, with one state representing a fast-growing growth cone state and the other a paused growth cone state. Owing to stochastic effects, even in an unchanging environment, model growth cones reversibly switch between growth and paused states. Our model further predicts that environmental signals could regulate axon growth rate by controlling the rates of switching between the two states. Our study presents a new conceptual understanding of growth cone switching behaviour, and suggests that axon guidance may be controlled by both cell-extrinsic factors and cell-intrinsic growth regulatory mechanisms.
26
Newsome, T. P., B. Asling, and B. J. Dickson. "Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics." Development 127, no. 4 (February 15, 2000): 851–60. http://dx.doi.org/10.1242/dev.127.4.851.
Full textAbstract:
During development of the adult Drosophila visual system, axons of the eight photoreceptors in each ommatidium fasciculate together and project as a single bundle towards the optic lobes of the brain. Within the brain, individual photoreceptor axons from each bundle then seek specific targets in distinct layers of the optic lobes. The axons of photoreceptors R1-R6 terminate in the lamina, while R7 and R8 axons pass through the lamina to terminate in separate layers of the medulla. To identify genes required for photoreceptor axon guidance, including those with essential functions during early development, we have devised a strategy for the simple and efficient generation of genetic mosaics in which mutant photoreceptor axons innervate a predominantly wild-type brain. In a large-scale saturation mutagenesis performed using this system, we recovered new alleles of the gene encoding the receptor tyrosine phosphatase PTP69D. PTP69D has previously been shown to function in the correct targeting of motor axons in the embryo and R1-R6 axons in the visual system. Here, we show that PTP69D is also required for correct targeting of R7 axons. Whereas mutant R1-R6 axons occasionally extend beyond their normal targets in the lamina, mutant R7 axons often fail to reach their targets in the medulla, stopping instead at the same level as the R8 axon. These targeting errors are difficult to reconcile with models in which PTP69D plays an instructive role in photoreceptor axon targeting, as previously proposed. Rather, we suggest that PTP69D plays a permissive role, perhaps reducing the adhesion of R1-R6 and R7 growth cones to the pioneer R8 axon so that they can respond independently to their specific targeting cues.
27
Hsu, Meng-Tsung, Chin-Lin Guo, Angela Y. Liou, Ting-Ya Chang, Ming-Chong Ng, Bogdan I. Florea, Herman S. Overkleeft, Yen-Lin Wu, Jung-Chi Liao, and Pei-Lin Cheng. "Stage-Dependent Axon Transport of Proteasomes Contributes to Axon Development." Developmental Cell 35, no. 4 (November 2015): 418–31. http://dx.doi.org/10.1016/j.devcel.2015.10.018.
Full text
28
Spead, Olivia, and Fabienne E. Poulain. "Trans-Axonal Signaling in Neural Circuit Wiring." International Journal of Molecular Sciences 21, no. 14 (July 21, 2020): 5170. http://dx.doi.org/10.3390/ijms21145170.
Full textAbstract:
The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon–axon interactions during the different steps of neural circuit formation.
29
Doyle, Daniel Z., Mandy M. Lam, Adel Qalieh, Yaman Qalieh, Alice Sorel, Owen H. Funk, and Kenneth Y. Kwan. "Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity." Proceedings of the National Academy of Sciences 118, no. 21 (May 19, 2021): e2100686118. http://dx.doi.org/10.1073/pnas.2100686118.
Full textAbstract:
Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.
30
Wojnacki, José, and Thierry Galli. "Membrane traffic during axon development." Developmental Neurobiology 76, no. 11 (March 24, 2016): 1185–200. http://dx.doi.org/10.1002/dneu.22390.
Full text
31
Hidalgo, A., J. Urban, and A. H. Brand. "Targeted ablation of glia disrupts axon tract formation in the Drosophila CNS." Development 121, no. 11 (November 1, 1995): 3703–12. http://dx.doi.org/10.1242/dev.121.11.3703.
Full textAbstract:
Glial cells are thought to play a role in growth cone guidance, both in insects and in vertebrates. In the developing central nervous system of the Drosophila embryo, the interface glia form a scaffold prior to the extension of the first pioneer growth cones. Growing axons appear to contact the glial scaffold as the axon tracts are established. We have used a novel technique for targeted cell ablation to kill the interface glia and thus to test their role in establishment of the embryonic axon tracts. We show that ablation of the interface glia early in development leads to a complete loss of the longitudinal axon tracts. Ablation of the glia later in embryonic development results in defects comprising weakening and loss of axon fascicles within the connectives. We conclude that the interface glia are required first for growth cone guidance in the formation of the longitudinal axon tracts in the Drosophila embryo and then either to direct the follower growth cones, or to maintain the longitudinal axon tracts.
32
Williams, Darren W., and David Shepherd. "Persistent larval sensory neurones are required for the normal development of the adult sensory afferent projections inDrosophila." Development 129, no. 3 (February 1, 2002): 617–24. http://dx.doi.org/10.1242/dev.129.3.617.
Full textAbstract:
We have tested the hypothesis that larval neurones guide growth of adult sensory axons in Drosophila. We show that ablation of larval sensory neurones causes defects in the central projections of adult sensory neurones. Spiralling axons and ectopic projections indicate failure in axon growth guidance. We show that larval sensory neurones are required for peripheral pathfinding, entry into the CNS and growth guidance within the CNS. Ablation of subsets of neurones shows that larval sensory neurones serve specific guidance roles. Dorsal neurones are required for axon guidance across the midline, whereas lateral neurones are required for posterior growth. We conclude that larval sensory neurones pioneer the assembly of sensory arrays in adults.
33
Pospichal, Marcie W., Sherre L. Florence, and Jon H. Kaas. "The postnatal development of geniculocortical axon arbors in owl monkeys." Visual Neuroscience 11, no. 1 (January 1994): 71–90. http://dx.doi.org/10.1017/s0952523800011123.
Full textAbstract:
AbstractTo characterize the postnatal development of geniculocortical axon arbor morphology in owl monkeys at a series of ages from birth to adulthood, individual arbors were bulk-filled with HRP in brain slice preparations and were reconstructed from serial sections. At all ages, cortical layers and sublayers were obvious. Presumed M or magnocellular arbors were largely confined to layer IVα, but they also extended into layer IIIc (IVB of Brodmann, 1909); presumed P or parvocellular arbors were almost exclusively confined to layer IVβ. Other axons that may reflect feedback projections from MT terminated in layer IIIc. Overall, M axon arbors increased in size and complexity from birth to adulthood with mean surface-view arbor areas ranging from 0.08 ± 0.01 mm2 in newborns to 0.24 ± 0.02 mm2 in adults. The developing P arbor areas were, on average, as large or larger than adult (newborn = 0.07 ± 0.01 mm2, adult = 0.047 ± 0.01 mm2; n.s.) but the arbors were somewhat less complex. Since the brain and area 17 increase in size postnatally, the proportion of area 17 subserved by each P arbor would decrease in postnatal development. Terminal boutons with immature features were evident in both M and P populations at all developmental ages. The results indicate that, while both LGN axon types in monkeys undergo morphological changes postnatally, M arbors appear to mature by increasing arbor size and terminal branching complexity, whereas P arbors increase in complexity but not in size. These distinct programs of axon arbor development suggest that the periods of susceptibility of geniculocortical axon arbors to postnatal influences of the environment, and the types of plastic responses they potentially exhibit, are class-specific.
34
Franze, Kristian. "Integrating Chemistry and Mechanics: The Forces Driving Axon Growth." Annual Review of Cell and Developmental Biology 36, no. 1 (October 6, 2020): 61–83. http://dx.doi.org/10.1146/annurev-cellbio-100818-125157.
Full textAbstract:
The brain is our most complex organ. During development, neurons extend axons, which may grow over long distances along well-defined pathways to connect to distant targets. Our current understanding of axon pathfinding is largely based on chemical signaling by attractive and repulsive guidance cues. These cues instruct motile growth cones, the leading tips of growing axons, where to turn and where to stop. However, it is not chemical signals that cause motion—motion is driven by forces. Yet our current understanding of the mechanical regulation of axon growth is very limited. In this review, I discuss the origin of the cellular forces controlling axon growth and pathfinding, and how mechanical signals encountered by growing axons may be integrated with chemical signals. This mechanochemical cross talk is an important but often overlooked aspect of cell motility that has major implications for many physiological and pathological processes involving neuronal growth.
35
Rodriguez-Gil, Diego J., Dianna L. Bartel, Austin W. Jaspers, Arie S. Mobley, Fumiaki Imamura, and Charles A. Greer. "Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons." Proceedings of the National Academy of Sciences 112, no. 18 (April 20, 2015): 5821–26. http://dx.doi.org/10.1073/pnas.1417955112.
Full textAbstract:
Odorant receptors (OR) are strongly implicated in coalescence of olfactory sensory neuron (OSN) axons and the formation of olfactory bulb (OB) glomeruli. However, when ORs are first expressed relative to basal cell division and OSN axon extension is unknown. We developed an in vivo fate-mapping strategy that enabled us to follow OSN maturation and axon extension beginning at basal cell division. In parallel, we mapped the molecular development of OSNs beginning at basal cell division, including the onset of OR expression. Our data show that ORs are first expressed around 4 d following basal cell division, 24 h after OSN axons have reached the OB. Over the next 6+ days the OSN axons navigate the OB nerve layer and ultimately coalesce in glomeruli. These data provide a previously unidentified perspective on the role of ORs in homophilic OSN axon adhesion and lead us to propose a new model dividing axon extension into two phases. Phase I is OR-independent and accounts for up to 50% of the time during which axons approach the OB and begin navigating the olfactory nerve layer. Phase II is OR-dependent and concludes as OSN axons coalesce in glomeruli.
36
Sur, M., M. Esguerra, P. E. Garraghty, M. F. Kritzer, and S. M. Sherman. "Morphology of physiologically identified retinogeniculate X- and Y-axons in the cat." Journal of Neurophysiology 58, no. 1 (July 1, 1987): 1–32. http://dx.doi.org/10.1152/jn.1987.58.1.1.
Full textAbstract:
1.We studied the morphology of individual, physiologically identified retinogeniculate axons in normal adult cats. The axons were recorded in the lateral geniculate nucleus or in the subjacent optic tract, characterized as X or Y by physiological criteria, penetrated, and injected with horseradish peroxidase. With subsequent application of appropriate histochemistry, the enzyme provides a complete label of the terminal arbors and parent trunks for morphological analysis. We have recovered for such analysis 26 X- and 25 Y-axons; of these, 14 X- and 12 Y-axons were studied in detail. 2. Within the optic tract, the parent trunk of every X-axon is located closer to the lateral geniculate nucleus and thus further from the pial surface than that of every Y-axon. This probably reflects the earlier development of X- than of Y-axons. Furthermore, the parent axon trunks of the X-axons are noticeably thinner than are those of the Y-axons. Every retinogeniculate X- and Y-axon in our sample branches within the optic tract. One of these branches heads dorsally to innervate the lateral geniculate nucleus and one heads medially and rostrally toward the midbrain, although none of these labeled axons were traced to a terminal arbor beyond the lateral geniculate nucleus. For Y-axons, all branches are of comparable diameter, but for X-axons, the branch heading toward the lateral geniculate nucleus is always noticeably thicker than is the branch directed toward the midbrain. 3. Every retinogeniculate X- and Y-axon produces the greatest portion of its terminal arbor in lamina A (if from the contralateral retina) or A1 (if from the ipsilateral retina). These arbors typically extend across most of the lamina along a projection line. Not a single terminal bouton from any axon was found in the inappropriate lamina A or A1 (i.e., in lamina A for ipsilaterally projecting axons or in lamina A1 for contralaterally projecting ones). Occasionally, an X-axon also innervates the medial interlaminar nucleus, and even more rarely does an X-axon innervate the C-laminae. In contrast, nearly all Y-axons from the contralateral retina branch to innervate part of the C-laminae (probably lamina C), and most from either retina also innervate the medial interlaminar nucleus. Although these details imply considerable variation in the overall pattern of retinogeniculate innervation for both X- and Y-axons, we found no physiological properties to correlate with this variation.(ABSTRACT TRUNCATED AT 400 WORDS)
37
Blagburn, J. M., D. J. Beadle, and D. B. Sattelle. "Development of synapses between identified sensory neurones and giant interneurones in the cockroach Periplaneta americana." Development 86, no. 1 (April 1, 1985): 227–46. http://dx.doi.org/10.1242/dev.86.1.227.
Full textAbstract:
The cereal afferent, giant interneurone pathway in Periplaneta americana was used as a model for synapse formation. The morphology of the two identified filiform hair sensory neurones (FHSNs) and of two giant interneurones (GI2 and GI3) was followed throughout embryogenesis by cobalt injection. The FHSN axons enter the CNS at the 45 % stage of embryogenesis, branch at 50 % and form complete arborizations by 70 %. The giant interneurones send out a primary dendrite at 45 %. Secondary branches form between 50 % and 60 % and elaboration of the branching pattern takes place until 80 % embryogenesis. At early stages the FHSN axons are within filopodial range of GI dendrites which may use these sensory processes as guidance cues. Synapse formation between the main FHSN axon shafts and GI dendrites was investigated by injection of the latter with HRP. From 55 % to 65 % the process is initiated by desmosome—like filopodial contacts, with subsequent vesicle clustering and formation of a small synaptic density. Numbers of contacts did not significantly increase after about 70 %, but the number of synapses doubled between 65 % and 75 %, with each GI process becoming postsynaptic to two FHSN synapses and the presynaptic densities lengthening to become bars. From 75 % embryogenesis to hatching there is a further small increase in synaptic bar length. In the first instar GI3 is postsynaptic to both FHSN axons, whereas GI2 forms very few synapses with the axon of the lateral FHSN (LFHSN). This imbalance of contacts is present throughout synaptogenesis, apart from some early filopodial contacts. GI3 forms synapses with the lateral side of the LFHSN axon from 60 % embryogenesis but these are totally absent at hatching. The growth of glia along this side of the axon during the last 30 % of development appears to be associated with degeneration of synapses in this region. Thus, as the dendrites of the GIs grow to form a miniature version of the adult without loss of branches, there is little evidence of an initial overproduction of FHSN—GI synapses. Similarly there is no evidence that GI2 forms ‘incorrect’ synapses with the axon of LFHSN. However, GI3 contacts are removed from an inappropriate region of a correct synaptic partner, LFHSN.
38
Muller, K. J., E. McGlade-McCulloh, and A. Mason. "Tinkering with successful synapse regeneration in the leech: adding insult to injury." Journal of Experimental Biology 132, no. 1 (September 1, 1987): 207–21. http://dx.doi.org/10.1242/jeb.132.1.207.
Full textAbstract:
In the leech, synapse regeneration in adults and synapse formation during embryonic development can be studied in single, identifiable cells that make precise connections with their targets. Certain cellular components, such as synaptic targets and glia, were selectively destroyed to study how the regenerating axons locate their targets, what triggers axons to start growing and what stops them. The results showed that glia and targets play only a limited role in synapse regeneration and in axon degeneration. For example, contact with the synaptic target may inhibit sprouting and availability of targets may promote it. Comparative studies on axon growth and synapse formation by interneurones in embryos showed that regeneration does not simply recapitulate embryonic development. There are clearly separate constraints on the two processes. Axon survival is a different problem. Although isolated axon segments can survive for up to a year in the leech, temperature is a major factor in survival. Axon segments in a tropical leech that regenerates synapses well at 31 degrees C degenerated within 2–3 weeks at this elevated temperature, even when regeneration was prevented. In similar leeches at room temperature (22 degrees C), segments survived for months. Overall, results in the leech support the idea that degeneration as well as regeneration share fundamental mechanisms with other invertebrates and the vertebrates, including mammals. Perhaps long-lived axon segments and other features of the leech that speed or encourage functional regeneration can now be made to operate in repair of the mammalian nervous system.
39
O'Leary, D. D. M., C. D. Heffner, L. Kutka, L. López-Mascaraque, A. Missias, and B. S. Reinoso. "A target-derived chemoattractant controls the development of the corticopontine projection by a novel mechanism of axon targeting." Development 113, Supplement_2 (April 1, 1991): 123–30. http://dx.doi.org/10.1242/dev.113.supplement_2.123.
Full textAbstract:
Here, we review our studies in rats of target recognition by developing cortical axons focusing on their innervation of the basilar pons, a major hindbrain target. The corticopontine projection develops by a ‘delayed interstitial budding’ of collaterals from layer 5 corticospinal axons, rather than by a direct ingrowth of primary axons or by bifurcation of the growth cone. Branches form de novo from the axon cylinder in the pathway overlying the basilar pons and extend directly into it. Cocultures of cortex and basilar pons in 3-dimensional collagen matrices show that a diffusible chemotropic signal released by the basilar pons directs the growth of collateral branches from layer 5 axons in a target and neuron specific manner. ‘Delayed’ co-cultures suggest that a diffusible, pontine-derived signal also initiates the selective branching of layer 5 axons. In vivo experiments support this chemotropic mechanism. First, corticospinal axons form collateral branches at novel locations directly over ectopic aggregations of basilar pontine neurons induced by X-irradiation; no branches form at positions that would normally overlie the appropriate region of basilar pons which is absent because of the X-irradiation. Thus, the basilar pons, rather than local cues in the axon pathway, appears to control the location of corticospinal axon branching. Second, in a series of experiments in which different subsets of corticospinal axons are prevented from innervating the basilar pons, remaining corticospinal axons extend collaterals in a directed manner to regions of the basilar pons deprived of cortical input, a behavior consistent with a response to a diffusible chemoattractant emanating from these regions. In conclusion, our findings suggest that a diffusible, target-derived chemotropic molecule(s) underlies target recognition in this developing system by initiating the formation and directing the growth of pontine collateral branches of primary layer 5 corticospinal axons.
40
Petrova, Veselina, Bart Nieuwenhuis, James W. Fawcett, and Richard Eva. "Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury." International Journal of Molecular Sciences 22, no. 4 (February 11, 2021): 1798. http://dx.doi.org/10.3390/ijms22041798.
Full textAbstract:
Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.
41
Preuss, T., and W. F. Gilly. "Role of prey-capture experience in the development of the escape response in the squid Loligo opalescens: a physiological correlate in an identified neuron." Journal of Experimental Biology 203, no. 3 (February 1, 2000): 559–65. http://dx.doi.org/10.1242/jeb.203.3.559.
Full textAbstract:
Although extensively used for biophysical studies, the squid giant axon system remains largely unexplored in regard to in vivo function and modulation in any biologically relevant context. Here we show that successful establishment of the recruitment pattern for the giant axon in the escape response elicited by a brief electrical stimulus depends on prey-capture experience early in life. Juvenile squid fed only slow-moving, easy-to-capture prey items (Artemia salina) develop deficits in coordinating activity in the giant axon system with that of a parallel set of non-giant motor axons during escape responses. These deficits are absent in cohorts fed fast-moving, challenging prey items (copepods). These results suggest that the acquisition of inhibitory control over the giant axon system is experience-dependent and that both prey-capture and escape behavior depend on this control.
42
Chen, Shih-Yu, Chun-Ta Ho, Wei-Wen Liu, Mark Lucanic, Hsiu-Ming Shih, Pei-Hsin Huang, and Hwai-Jong Cheng. "Regulation of axon repulsion by MAX-1 SUMOylation and AP-3." Proceedings of the National Academy of Sciences 115, no. 35 (August 13, 2018): E8236—E8245. http://dx.doi.org/10.1073/pnas.1804373115.
Full textAbstract:
During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5–mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5–mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3. Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3. Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3–mediated trafficking and degradation of UNC-5 receptors during axon guidance.
43
Anderson, R. B., and B. Key. "Novel guidance cues during neuronal pathfinding in the early scaffold of axon tracts in the rostral brain." Development 126, no. 9 (May 1, 1999): 1859–68. http://dx.doi.org/10.1242/dev.126.9.1859.
Full textAbstract:
A scaffold of axons consisting of a pair of longitudinal tracts and several commissures is established during early development of the vertebrate brain. We report here that NOC-2, a cell surface carbohydrate, is selectively expressed by a subpopulation of growing axons in this scaffold in Xenopus. NOC-2 is present on two glycoproteins, one of which is a novel glycoform of the neural cell adhesion molecule N-CAM. When the function of NOC-2 was perturbed using either soluble carbohydrates or anti-NOC-2 antibodies, axons expressing NOC-2 exhibited aberrant growth at specific points in their pathway. NOC-2 is the first-identified axon guidance molecule essential for development of the axon scaffold in the embryonic vertebrate brain.
44
Misgeld, Thomas. "Death of an axon: studying axon loss in development and disease." Histochemistry and Cell Biology 124, no. 3-4 (August 13, 2005): 189–96. http://dx.doi.org/10.1007/s00418-005-0036-6.
Full text
45
Birgbauer, E., C. A. Cowan, D. W. Sretavan, and M. Henkemeyer. "Kinase independent function of EphB receptors in retinal axon pathfinding to the optic disc from dorsal but not ventral retina." Development 127, no. 6 (March 15, 2000): 1231–41. http://dx.doi.org/10.1242/dev.127.6.1231.
Full textAbstract:
Optic nerve formation requires precise retinal ganglion cell (RGC) axon pathfinding within the retina to the optic disc, the molecular basis of which is not well understood. At CNS targets, interactions between Eph receptor tyrosine kinases on RGC axons and ephrin ligands on target cells have been implicated in formation of topographic maps. However, studies in chick and mouse have shown that both Eph receptors and ephrins are also expressed within the retina itself, raising the possibility that this receptor-ligand family mediates aspects of retinal development. Here, we more fully document the presence of specific EphB receptors and B-ephrins in embryonic mouse retina and provide evidence that EphB receptors are involved in RGC axon pathfinding to the optic disc. We find that as RGC axons begin this pathfinding process, EphB receptors are uniformly expressed along the dorsal-ventral retinal axis. This is in contrast to the previously reported high ventral-low dorsal gradient of EphB receptors later in development when RGC axons map to CNS targets. We show that mice lacking both EphB2 and EphB3 receptor tyrosine kinases, but not each alone, exhibit increased frequency of RGC axon guidance errors to the optic disc. In these animals, major aspects of retinal development and cellular organization appear normal, as do the expression of other RGC guidance cues netrin, DCC, and L1. Unexpectedly, errors occur in dorsal but not ventral retina despite early uniform or later high ventral expression of EphB2 and EphB3. Furthermore, embryos lacking EphB3 and the kinase domain of EphB2 do not show increased errors, consistent with a guidance role for the EphB2 extracellular domain. Thus, while Eph kinase function is involved in RGC axon mapping in the brain, RGC axon pathfinding within the retina is partially mediated by EphB receptors acting in a kinase-independent manner.
46
Taylor, Jeremy S. H. "The early development of the frog retinotectal projection." Development 113, Supplement_2 (April 1, 1991): 95–104. http://dx.doi.org/10.1242/dev.113.supplement_2.95.
Full textAbstract:
The guidance of retinal ganglion cell axons has been investigated in embryos of the frog Xenopus. During the initial development of the brain a series of axon tracts are laid down forming a basic ‘scaffold’ or framework. Retinal axons grow through one of these tracts, the tract of the post-optic commissure (tPOC). This is the only tract that extends through the rostral part of the brain at these early stages of development. The origin and development of the tPOC has been studied using antibodies which label neurons at their earliest stages of differentiation. The first sign of the tPOC is a chain of neurons which differentiate simultaneously in the caudolateral part of the diencephalon. Axons from these neurons grow the short distance between adjacent cells interlinking the chain to form a descending tract. A series of other axon projections are then added to the tPOC, each of which is segregated into a particular subregion of the tract. Retinal axons are added to the tract approximately 18 h after its formation. They grow in the sub-pial part of the tract and always occupy the rostralmost edge. Retinal axons follow the tract to the region of the developing tectum where they leave, turn dorsally, and terminate. The reliance of retinal axons on this pre-existing pathway has been demonstrated by experimentally altering the course of the tPOC during its early development. The caudo-lateral wall of the diencephalon has been rotated through 90° at a stage just before the tPOC neurons differentiate. Confirmation of the predicted alteration in the course of the tPOC has been made using immunocytochemistry. In such manipulated brains, retinal axons maintain their strong affinity for the rostral edge of the tPOC, following its altered course through the diencephalon.
47
Umeda, Kentaro, Nariaki Iwasawa, Manabu Negishi, and Izumi Oinuma. "A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner." Molecular Biology of the Cell 26, no. 10 (May 15, 2015): 1957–70. http://dx.doi.org/10.1091/mbc.e15-01-0039.
Full textAbstract:
Precise wiring patterns of axons are among the remarkable features of neuronal circuit formation, and establishment of the proper neuronal network requires control of outgrowth, branching, and guidance of axons. R-Ras is a Ras-family small GTPase that has essential roles in multiple phases of axonal development. We recently identified afadin, an F-actin–binding protein, as an effector of R-Ras mediating axon branching through F-actin reorganization. Afadin comprises two isoforms—l-afadin, having the F-actin–binding domain, and s-afadin, lacking the F-actin–binding domain. Compared with l-afadin, s-afadin, the short splicing variant of l-afadin, contains RA domains but lacks the F-actin–binding domain. Neurons express both isoforms; however, the function of s-afadin in brain remains unknown. Here we identify s-afadin as an endogenous inhibitor of cortical axon branching. In contrast to the abundant and constant expression of l-afadin throughout neuronal development, the expression of s-afadin is relatively low when cortical axons branch actively. Ectopic expression and knockdown of s-afadin suppress and promote branching, respectively. s-Afadin blocks the R-Ras–mediated membrane translocation of l-afadin and axon branching by inhibiting the binding of l-afadin to R-Ras. Thus s-afadin acts as a dominant-negative isoform in R-Ras-afadin–regulated axon branching.
48
Goslin, K., and G. Banker. "Rapid changes in the distribution of GAP-43 correlate with the expression of neuronal polarity during normal development and under experimental conditions." Journal of Cell Biology 110, no. 4 (April 1, 1990): 1319–31. http://dx.doi.org/10.1083/jcb.110.4.1319.
Full textAbstract:
Hippocampal neurons growing in culture initially extend several, short minor processes that have the potential to become either axons or dendrites. The first expression of polarity occurs when one of these minor processes begins to elongate rapidly, becoming the axon. Before axonal outgrowth, the growth-associated protein GAP-43 is distributed equally among the growth cones of the minor processes; it is preferentially concentrated in the axonal growth cone once polarity has been established (Goslin, K., D. Schreyer, J. Skene, and G. Banker. 1990. J. Neurosci. 10:588-602). To determine when the selective segregation of GAP-43 begins, we followed individual cells by video microscopy, fixed them as soon as the axon could be distinguished, and localized GAP-43 by immunofluorescence microscopy. Individual minor processes acquired axonal growth characteristics within a period of 30-60 min, and GAP-43 became selectively concentrated to the growth cones of these processes with an equally rapid time course. We also examined changes in the distribution of GAP-43 after transection of the axon. After an axonal transection that is distant from the soma, neuronal polarity is maintained, and the original axon begins to regrow almost immediately. In such cases, GAP-43 became selectively concentrated in the new axonal growth cone within 12-30 min. In contrast, when the axon is transected close to the soma, polarity is lost; the original axon rarely regrows, and there is a significant delay before a new axon emerges. Under these circumstances, GAP-43 accumulated in the new growth cone much more slowly, suggesting that its ongoing selective routing to the axon had been disrupted by the transection. These results demonstrate that the selective segregation of GAP-43 to the growth cone of a single process is closely correlated with the acquisition of axonal growth characteristics and, hence, with the expression of polarity.
49
Bovolenta, P., and J. Dodd. "Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord." Development 109, no. 2 (June 1, 1990): 435–47. http://dx.doi.org/10.1242/dev.109.2.435.
Full textAbstract:
The floor plate of the embryonic rat spinal cord has been proposed to act as an intermediate target that plays a role in the pattern of extension of commissural axons. To begin to examine the role of the floor plate in axon guidance at the midline, we have studied the precision of the commissural axon projection to and across the floor plate during development. To delineate the pathway, the fluorescent carbocyanine dye, Di-I, has been used as a probe. We show that commissural axons traverse the floor plate and turn rostrally at its contralateral border with remarkable precision. Axons were not observed to turn ipsilaterally and turned only upon reaching the contralateral edge of the floor plate. Virtually all commissural axons follow this route. The morphology of commissural growth cones was also examined. As they encountered the floor plate, commissural growth cones became larger and increased in complexity. The reorientation of axons in register with the floor plate boundary and the change in the morphological properties of commissural growth cones as they traverse the midline suggest that the floor plate may act as a guidepost with functions similar to cells that have been implicated in axon guidance in invertebrates.
50
Shao, Xueying, Maja Højvang Sørensen, Xingyu Xia, Chao Fang, Tsz Hin Hui, Raymond Chuen Chung Chang, Zhiqin Chu, and Yuan Lin. "Beading of injured axons driven by tension- and adhesion-regulated membrane shape instability." Journal of The Royal Society Interface 17, no. 168 (July 2020): 20200331. http://dx.doi.org/10.1098/rsif.2020.0331.
Full textAbstract:
The formation of multiple beads along an injured axon will lead to blockage of axonal transport and eventually neuron death, and this has been widely recognized as a hallmark of nervous system degeneration. Nevertheless, the underlying mechanisms remain poorly understood. Here, we report a combined experimental and theoretical study to reveal key factors governing axon beading. Specifically, by transecting well-developed axons with a sharp atomic force microscope probe, significant beading of the axons was triggered. We showed that adhesion was not required for beading to occur, although when present strong axon–substrate attachments seemed to set the locations for bead formation. In addition, the beading wavelength, representing the average distance between beads, was found to correlate with the size and cytoskeleton integrity of axon, with a thinner axon or a disrupted actin cytoskeleton both leading to a shorter beading wavelength. A model was also developed to explain these observations which suggest that axon beading originates from the shape instability of the membrane and is driven by the release of work done by axonal tension as well as the reduction of membrane surface energy. The beading wavelength predicted from this theory was in good agreement with our experiments under various conditions. By elucidating the essential physics behind axon beading, the current study could enhance our understanding of how axonal injury and neurodegeneration progress as well as provide insights for the development of possible treatment strategies.