Genes that guide growth cones along the C. elegans ventral nerve cord

Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2571-2580 ◽  
Author(s):  
B. Wightman ◽  
R. Baran ◽  
G. Garriga
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
System Development ◽  
Growth Cones ◽  
Nervous System Development ◽  
Nerve Bundle ◽  
C Elegans ◽  
Bundle Structure

During nervous system development, growth cone pioneering and fasciculation contribute to nerve bundle structure. Pioneer growth cones initially navigate along neuroglia to establish an axon scaffold that guides later extending growth cones. In C. elegans, the growth cone of the PVPR neuron pioneers the left ventral nerve cord bundle, providing a path for the embryonic extensions of the PVQL and AVKR growth cones. Later during larval development, the HSNL growth cone follows cues in the left ventral nerve cord bundle provided by the PVPR and PVQL axons. Here we show that mutations in the genes enu-1, fax-1, unc-3, unc-30, unc-42 and unc-115 disrupt pathfinding of growth cones along the left ventral nerve cord bundle. Our results indicate that unc-3 and unc-30 function in ventral nerve cord pioneering and that enu-1, fax-1, unc-42 and unc-115 function in recognition of the PVPR and PVQL axons by the AVKR and HSNL growth cones.

scholarly journals The neuron pioneering the ventral nerve cord does not follow the common pathway of neurogenesis in the polychaete Malacoceros fuliginosus

2020 ◽  
Author(s):  
Suman Kumar ◽  
Sharat Chandra Tumu ◽  
Conrad Helm ◽  
Harald Hausen
Keyword(s):  
Nervous System ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
System Development ◽  
Nervous System Development ◽  
Whole Body ◽  
Hierarchical Level ◽  
Major Influence ◽  
Extrinsic Factors ◽  
Pioneer Neurons

Abstract Background: Nervous system development is an interplay of many processes: the formation of individual neurons which depends on whole-body and local patterning processes and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the early steps of nervous system development in the annelid Malacoceros fuliginosus.Results: We find that the first pioneer neurons are already in place in the anterior and posterior pole when broad neurogenesis is just starting. They do not express serotonin or FMRFamide which are commonly used markers in studies on nervous system architecture. A single posterior neuron prefigures the main course of the ventral nerve cord and this mode is probably ancestral for majority of annelids. Notably, none of the studied sox and proneural genes, which are commonly involved in the generation of neurons, is expressed by this important neuron. The only transcription factor we found expressed is Brn3, which likely acts on a low hierarchical level.Conclusions: We propose that the annelid ventral nerve cord pioneer neuron follows a highly divergent course of neurogenesis. The lack of Sox and proneural transcription factors, which are usually under control of patterning cell-extrinsic factors suggest a major influence of inherited cell-intrinsic properties on the development of this cell. Though cell-autonomous specification is generally an important pathway in the early development of spirally cleaving animals, its relevance for nervous system development is poorly understood. Our data suggest that closer investigation of the specification of pioneer neurons in animals featuring spiral cleavage will be highly informative to obtain a better understanding of how nervous systems form and evolve.

scholarly journals Regulation of miRNAs during Retinoic Acid-Induced Regeneration of a Molluscan Central Nervous System

2018 ◽  
Author(s):  
Sarah E. Walker ◽  
Gaynor E. Spencer ◽  
Alexsandr Necakov ◽  
Robert L. Carlone
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Lymnaea Stagnalis ◽  
System Development ◽  
Growth Cones ◽  
Nervous System Development ◽  
Biologically Active ◽  
Neuronal Outgrowth ◽  
First Time

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

scholarly journals Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development in C. elegans

2018 ◽  
Author(s):  
Lauren Bayer Horowitz ◽  
Julia P. Brandt ◽  
Niels Ringstad
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
P38 Map Kinase ◽  
Dependent Manner ◽  
Neuron Development ◽  
C Elegans ◽  
Chemosensory Neuron ◽  
Insulin Receptor Signaling ◽  
Activity Dependent

AbstractNervous system development is instructed both by genetic programs and activity-dependent refinement of gene expression and connectivity. How these mechanisms are integrated remains poorly understood. Here, we report that the regulated release of insulin-like peptides (ILPs) during development of the C. elegans nervous system accomplishes such an integration. We find that the p38 MAP kinase PMK-3, which is required for the differentiation of chemosensory BAG neurons, functions by limiting expression of an autocrine ILP signal that represses a chemosensory-neuron fate. ILPs are released from BAGs in an activity-dependent manner during embryonic development, and regulate neurodifferentiation through a non-canonical insulin receptor signaling pathway. The differentiation of a specialized neuron-type is, therefore, coordinately regulated by a genetic program that controls ILP expression and by neural activity, which regulates ILP release. Autocrine signals of this kind may have general and conserved functions as integrators of deterministic genetic programs with activity-dependent mechanisms during neurodevelopment.

scholarly journals Unique Responses of Differentiating Neuronal Growth Cones to Inhibitory Cues Presented by Oligodendrocytes

1998 ◽  
Vol 142 (1) ◽  
pp. 191-202 ◽  
Author(s):  
A. Shibata ◽  
M.V. Wright ◽  
S. David ◽  
L. McKerracher ◽  
P.E. Braun ◽  
...  
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Dendritic Growth ◽  
System Development ◽  
Axonal Growth ◽  
Growth Cones ◽  
Nervous System Development ◽  
Environmental Cues ◽  
Growth Cone Collapse ◽  
Neuronal Growth Cones

During central nervous system development, neurons differentiate distinct axonal and dendritic processes whose outgrowth is influenced by environmental cues. Given the known intrinsic differences between axons and dendrites and that little is known about the response of dendrites to inhibitory cues, we tested the hypothesis that outgrowth of differentiating axons and dendrites of hippocampal neurons is differentially influenced by inhibitory environmental cues. A sensitive growth cone behavior assay was used to assess responses of differentiating axonal and dendritic growth cones to oligodendrocytes and oligodendrocyte- derived, myelin-associated glycoprotein (MAG). We report that >90% of axonal growth cones collapsed after contact with oligodendrocytes. None of the encounters between differentiating, MAP-2 positive dendritic growth cones and oligodendrocytes resulted in growth cone collapse. The insensitivity of differentiating dendritic growth cones appears to be acquired since they develop from minor processes whose growth cones are inhibited (nearly 70% collapse) by contact with oligodendrocytes. Recombinant MAG(rMAG)-coated beads caused collapse of 72% of axonal growth cones but only 29% of differentiating dendritic growth cones. Unlike their response to contact with oligodendrocytes, few growth cones of minor processes were inhibited by rMAG-coated beads (20% collapsed). These results reveal the capability of differentiating growth cones of the same neuron to partition the complex molecular terrain they navigate by generating unique responses to particular inhibitory environmental cues.

scholarly journals Regulation of Gliogenesis by lin-32/Atoh1 in Caenorhabditis elegans

2020 ◽  
Vol 10 (9) ◽  
pp. 3271-3278 ◽  
Author(s):  
Albert Zhang ◽  
Kentaro Noma ◽  
Dong Yan
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Molecular Mechanisms ◽  
System Development ◽  
Nervous System Development ◽  
Proneural Gene ◽  
C Elegans ◽  
Fundamental Process ◽  
Mutant Phenotypes

Abstract The regulation of gliogenesis is a fundamental process for nervous system development, as the appropriate glial number and identity is required for a functional nervous system. To investigate the molecular mechanisms involved in gliogenesis, we used C. elegans as a model and identified the function of the proneural gene lin-32/Atoh1 in gliogenesis. We found that lin-32 functions during embryonic development to negatively regulate the number of AMsh glia. The ectopic AMsh cells at least partially arise from cells originally fated to become CEPsh glia, suggesting that lin-32 is involved in the specification of specific glial subtypes. Moreover, we show that lin-32 acts in parallel with cnd-1/ NeuroD1 and ngn-1/ Neurog1 in negatively regulating an AMsh glia fate. Furthermore, expression of murine Atoh1 fully rescues lin-32 mutant phenotypes, suggesting lin-32/Atoh1 may have a conserved role in glial specification.

scholarly journals Unraveling Axon Guidance during Axotomy and Regeneration

2021 ◽  
Vol 22 (15) ◽  
pp. 8344
Author(s):  
Miguel E. Domínguez-Romero ◽  
Paula G. Slater
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Neuronal Development ◽  
System Development ◽  
Nervous System Development ◽  
Signaling Cascades ◽  
Final Destination ◽  
Guidance Cues ◽  
The Central Nervous System ◽  
Do So

During neuronal development and regeneration axons extend a cytoskeletal-rich structure known as the growth cone, which detects and integrates signals to reach its final destination. The guidance cues “signals” bind their receptors, activating signaling cascades that result in the regulation of the growth cone cytoskeleton, defining growth cone advance, pausing, turning, or collapse. Even though much is known about guidance cues and their isolated mechanisms during nervous system development, there is still a gap in the understanding of the crosstalk between them, and about what happens after nervous system injuries. After neuronal injuries in mammals, only axons in the peripheral nervous system are able to regenerate, while the ones from the central nervous system fail to do so. Therefore, untangling the guidance cues mechanisms, as well as their behavior and characterization after axotomy and regeneration, are of special interest for understanding and treating neuronal injuries. In this review, we present findings on growth cone guidance and canonical guidance cues mechanisms, followed by a description and comparison of growth cone pathfinding mechanisms after axotomy, in regenerative and non-regenerative animal models.

scholarly journals Regulation of Growth Cone Actin Dynamics by ADF/Cofilin

2003 ◽  
Vol 51 (4) ◽  
pp. 411-420 ◽  
Author(s):  
Ravine A. Gungabissoon ◽  
James R. Bamburg
Keyword(s):  
Actin Cytoskeleton ◽  
Growth Cone ◽  
Rho Gtpases ◽  
System Development ◽  
Cell Types ◽  
Growth Cones ◽  
Nervous System Development ◽  
Actin Dynamics ◽  
Target Cells ◽  
Lim Kinase

Nervous system development is reliant on neuronal pathfinding, the process in which axons are guided to their target cells by specific extracellular cues. The ability of neurons to extend over long distances in response to environmental guidance signals is made possible by the growth cone, a highly motile structure found at the end of neuronal processes. Growth cones detect directional cues and respond with either attractive or repulsive movements. The motility of growth cones is dependent on rapid reorganization of the actin cytoskeleton, presumably mediated by actin-associated proteins under the control of incoming guidance signals. This article reviews how one such family of proteins, the ADF/cofilins, are emerging as key regulators of growth cone actin dynamics. These proteins are essential for rapid actin turnover in a variety of different cell types. ADF/cofilins are heavily co-localized with actin in growth cones and are necessary for neurite outgrowth. ADF/cofilin activities are regulated through reversible phosphorylation by LIM kinases and slingshot phosphatases. LIM kinases are downstream effectors of the Rho GTPases Rho, Rac, and Cdc42. Growing evidence suggests that extracellular guidance cues may locally alter actin dynamics by regulating the activity of LIM kinase and ADF/cofilin phosphatases via the Rho GTPases. In this way, ADF/cofilins and their upstream effectors may be pivotal to our understanding of how guidance information is translated into physical alterations of the growth cone actin cytoskeleton.

scholarly journals Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 4121-4131 ◽  
Author(s):  
K.P. Menon ◽  
K. Zinn
Keyword(s):  
Nervous System ◽  
Tyrosine Kinase ◽  
Growth Cone ◽  
Growth Cones ◽  
Nervous System Development ◽  
The Body ◽  
Individual Growth ◽  
Kinase Inhibition ◽  
Tyrosine Kinase Inhibition ◽  
Herbimycin A

Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development. We have examined the roles of tyrosine kinase activity in programming growth cone guidance decisions in an intact nervous system in which neurons can be individually identified. We applied the tyrosine kinase inhibitors herbimycin A and genistein to whole 40% grasshopper embryos placed in medium, or injected the inhibitors into intact grasshopper eggs. Both inhibitors caused interneuronal axons that normally would grow along the longitudinal connectives to instead leave the central nervous system (CNS) within the segmental nerve root and grow out toward the body wall muscles. In addition, herbimycin A produced pathfinding errors in which many longitudinal axons crossed the CNS midline. To study how this drug affected guidance decisions made by individual growth cones, we dye-filled the pCC interneuron, which normally extends an axon anteriorly along the ipsilateral longitudinal connective. In the presence of herbimycin A, the pCC growth cone was redirected across the anterior commissure. These phenotypes suggest that tyrosine kinase inhibition blocks a signaling mechanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline.

scholarly journals Characterization of RQ1, a mutant involved in nervous system development in C. Elegans

2021 ◽  
Author(s):  
Matthew M Bueno de Mesquita
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Wild Type ◽  
Directional Information ◽  
Double Stranded Rna ◽  
Knock Out ◽  
C Elegans ◽  
Strong Candidate

During the development of the nervous system, guidance cues provide directional information to the growth cones of migrating axons. In C. elegans, ventral to dorsal migration is in part mediated by the ligand UNC-6 and its receptor UNC-5. In an UNC-5 null mutant the DA and DB motor neuron axons fail to migrate in a wild type manner to the dorsal cord, despite initial dorsalward outgrowth from the cell bodies. A genetic enhancer screen was conducted in an UNC-5 null strain and one mutant, rq1, was found to have increased axon guidance defects. To identify the mutated gene in rq1, microinjection experiments were performed and were able to rescue two rq1 phontypes. RNAi experiments were performed where double stranded RNA corresponding to all the genes in the region were used individually to knock out the transcripts. Several of these were able to phenocopy the defects of rq1. The rq1 mutation could be located in any one of five genes known to be present on the rescuing cosmid while combined results implicate three strong candidate genes, M03C11.8, H04D03.1 and H04D03.4.

scholarly journals The C. elegans gene vab-8 guides posteriorly directed axon outgrowth and cell migration

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 671-682 ◽  
Author(s):  
B. Wightman ◽  
S.G. Clark ◽  
A.M. Taskar ◽  
W.C. Forrester ◽  
A.V. Maricq ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Growth Cone ◽  
Growth Cones ◽  
Body Axis ◽  
Axon Outgrowth ◽  
Common Mechanism ◽  
C Elegans

The assembly of the nervous system in the nematode C. elegans requires the directed migrations of cells and growth comes along the anteroposterior and dorsoventral body axis. We show here that the gene vab-8 is essential for most posteriorly directed migrations of cells and growth cones. Mutations in vab-8 disrupt fourteen of seventeen posteriorly directed migrations, but only two of seventeen anteriorly directed and dorsoventral migrations. For two types of neurons that extend axons both anteriorly and posteriorly, vab-8 mutations disrupt only the growth of the posteriorly directed axon. vab-8 encodes two genetic activities that function in the guidance of different migrations. Our results suggest that most posteriorly directed cell and growth cone migrations are guided by a common mechanism involving the vab-8 gene.

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