Genes required for axon pathfinding and extension in the C. elegans nerve ring

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3679-3692 ◽  
Author(s):  
J.A. Zallen ◽  
S.A. Kirch ◽  
C.I. Bargmann
Keyword(s):  
Axon Guidance ◽  
Fluorescent Protein ◽  
System Development ◽  
Axon Growth ◽  
Ring Structure ◽  
Nervous System Development ◽  
Nerve Ring ◽  
Eph Receptor ◽  
Axon Extension ◽  
Growth Guidance

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.

scholarly journals Cbln1 regulates axon growth and guidance in multiple neural regions

2021 ◽  
Author(s):  
Sheng-Jian Ji ◽  
Peng Han ◽  
Yuanchu She ◽  
Zhuoxuan Yang ◽  
Mengru Zhuang ◽  
...  
Keyword(s):  
Nervous System ◽  
Axon Guidance ◽  
Neural Development ◽  
System Development ◽  
Axon Growth ◽  
Nervous System Development ◽  
Precise Control ◽  
Commissural Neurons ◽  
Guidance Cues ◽  
Guidance Cue

The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon guidance have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS). Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.

scholarly journals Harnessing PTEN’s Growth Potential in Neuronal Development and Disease

2020 ◽  
Vol 15 ◽  
pp. 263310552095905
Author(s):  
Joachim Fuchs ◽  
Britta J. Eickholt ◽  
George Leondaritis
Keyword(s):  
Neurodevelopmental Disorders ◽  
Neuronal Development ◽  
System Development ◽  
Transmembrane Protein ◽  
Nervous System Development ◽  
Growth Potential ◽  
Dependent Manner ◽  
Axon Extension ◽  
Growth Promoting ◽  
Spatiotemporal Control

PTEN is a powerful regulator of neuronal growth. It globally suppresses axon extension and branching during both nervous system development and regeneration, by antagonizing growth-promoting PI3K/PI(3,4,5)P3 signaling. We recently identified that the transmembrane protein PRG2/LPPR3 functions as a modulator of PTEN function during axon morphogenesis. Our work demonstrates that through inhibition of PTEN activity, PRG2 stabilizes membrane PI(3,4,5)P3. In turn, PRG2 deficiency attenuates the formation of branches in a PTEN-dependent manner, albeit without affecting the overall growth capacity of extending axons. Thus, PRG2 is poised to temporally and locally relieve growth suppression mediated by PTEN in neurons and, in effect, to redirect growth specifically to axonal branches. In this commentary, we discuss potential implications and unresolved questions regarding the regulation of axonal PTEN in neurons. Given their widespread implication during neuronal development and regeneration, identification of mechanisms that confer spatiotemporal control of PTEN may unveil new approaches to reprogram PI3K signaling in neurodevelopmental disorders and regeneration research.

scholarly journals The Fine Art of Writing a Message: RNA Metabolism in the Shaping and Remodeling of the Nervous System

2021 ◽  
Vol 14 ◽  
Author(s):  
María Landínez-Macías ◽  
Olivier Urwyler
Keyword(s):  
Nervous System ◽  
Binding Proteins ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Axon Growth ◽  
Rna Metabolism ◽  
Nervous System Development ◽  
Protein Isoforms ◽  
Growth Guidance

Neuronal morphogenesis, integration into circuits, and remodeling of synaptic connections occur in temporally and spatially defined steps. Accordingly, the expression of proteins and specific protein isoforms that contribute to these processes must be controlled quantitatively in time and space. A wide variety of post-transcriptional regulatory mechanisms, which act on pre-mRNA and mRNA molecules contribute to this control. They are thereby critically involved in physiological and pathophysiological nervous system development, function, and maintenance. Here, we review recent findings on how mRNA metabolism contributes to neuronal development, from neural stem cell maintenance to synapse specification, with a particular focus on axon growth, guidance, branching, and synapse formation. We emphasize the role of RNA-binding proteins, and highlight their emerging roles in the poorly understood molecular processes of RNA editing, alternative polyadenylation, and temporal control of splicing, while also discussing alternative splicing, RNA localization, and local translation. We illustrate with the example of the evolutionary conserved Musashi protein family how individual RNA-binding proteins are, on the one hand, acting in different processes of RNA metabolism, and, on the other hand, impacting multiple steps in neuronal development and circuit formation. Finally, we provide links to diseases that have been associated with the malfunction of RNA-binding proteins and disrupted post-transcriptional regulation.

scholarly journals A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-26 ◽  
Author(s):  
Xiyue Ye ◽  
Yan Qiu ◽  
Yuqing Gao ◽  
Dong Wan ◽  
Huifeng Zhu
Keyword(s):  
Axon Guidance ◽  
Signaling Pathways ◽  
Growth Cone ◽  
System Development ◽  
Dynamic Structure ◽  
Nervous System Development ◽  
Axonal Projections ◽  
Directional Decisions ◽  
Intrinsic Dynamic

A fundamental feature of both early nervous system development and axon regeneration is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. In the navigation process where the nerves grow toward their targets, the growth cones, which locate at the tips of axons, sense the environment surrounding them, including varies of attractive or repulsive molecular cues, then make directional decisions to adjust their navigation journey. The turning ability of a growth cone largely depends on its highly dynamic skeleton, where actin filaments and microtubules play a very important role in its motility. In this review, we summarize some possible mechanisms underlying growth cone motility, relevant molecular cues, and signaling pathways in axon guidance of previous studies and discuss some questions regarding directions for further studies.

Persistent larval sensory neurones are required for the normal development of the adult sensory afferent projections inDrosophila

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 617-624
Author(s):  
Darren W. Williams ◽  
David Shepherd
Keyword(s):  
Axon Guidance ◽  
Normal Development ◽  
Axon Growth ◽  
Central Projections ◽  
Sensory Neurones ◽  
Afferent Projections ◽  
Sensory Axons ◽  
Growth Guidance

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.

scholarly journals Male Differentiation in the Marine Copepod Oithona nana Reveals the Development of a New Nervous Ganglion and Lin12-Notch-Repeat Protein-Associated Proteolysis

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 657
Author(s):  
Kevin Sugier ◽  
Romuald Laso-Jadart ◽  
Benoît Vacherie ◽  
Jos Käfer ◽  
Laurie Bertrand ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Interaction ◽  
System Development ◽  
Interaction Network ◽  
Nervous System Development ◽  
Protein Coding ◽  
Protein Protein Interaction ◽  
Marine Copepod ◽  
Growth Guidance ◽  
Male Specific

Copepods are among the most numerous animals, and they play an essential role in the marine trophic web and biogeochemical cycles. The genus Oithona is described as having the highest density of copepods. The Oithona male paradox describes the activity states of males, which are obliged to alternate between immobile and mobile phases for ambush feeding and mate searching, respectively, while the female is less mobile and feeds less. To characterize the molecular basis of this sexual dimorphism, we combined immunofluorescence, genomics, transcriptomics, and protein–protein interaction approaches and revealed the presence of a male-specific nervous ganglion. Transcriptomic analysis showed male-specific enrichment for nervous system development-related transcripts. Twenty-seven Lin12-Notch Repeat domain-containing protein coding genes (LDPGs) of the 75 LDPGs identified in the genome were specifically expressed in males. Furthermore, some LDPGs coded for proteins with predicted proteolytic activity, and proteases-associated transcripts showed a male-specific enrichment. Using yeast double–hybrid assays, we constructed a protein–protein interaction network involving two LDPs with proteases, extracellular matrix proteins, and neurogenesis-related proteins. We also hypothesized possible roles of the LDPGs in the development of the lateral ganglia through helping in extracellular matrix lysis, neurites growth guidance, and synapses genesis.

Dual function of polysialic acid during zebrafish central nervous system development

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 4949-4958
Author(s):  
Monika Marx ◽  
Urs Rutishauser ◽  
Martin Bastmeyer
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Pattern ◽  
System Development ◽  
Polysialic Acid ◽  
Axon Growth ◽  
Nervous System Development ◽  
Dual Function ◽  
Central Nervous System Development ◽  
Posterior Commissure

Polysialic acid (PSA), a carbohydrate epitope attached to the neural cell adhesion molecule, serves as a modulator of axonal interactions during vertebrate nervous system development. We have used PSA-specific antibodies and whole-mount immunocytochemistry to describe the spatiotemporal expression pattern of PSA during zebrafish central nervous system development. PSA is transiently expressed on all cell bodies and, except for the posterior commissure, it is not found on axons. Floorplate cells in the spinal cord and hindbrain strongly express PSA throughout development. Enzymatic removal of PSA leads to a defasciculated growth pattern of the posterior commissure and also affects distinct subsets of commissural axons in the hindbrain, which fail to cross the midline. Whereas the disordered growth pattern of hindbrain commissures produced by PSA-removal could be mimicked by injections of soluble PSA, the growth of axons in the posterior commissure was unaffected by such treatment. These results suggest that there are distinct mechanisms for PSA action during axon growth and pathfinding in the developing zebrafish CNS.

scholarly journals Functional role of pax6 in eye and central nervous system development in the annelid Capitella teleta

2018 ◽  
Author(s):  
Marleen Klann ◽  
Elaine C. Seaver
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Functional Role ◽  
System Development ◽  
Axon Growth ◽  
Nervous System Development ◽  
Loss Of Function ◽  
Downstream Target ◽  
Capitella Teleta

AbstractThe transcription factor Pax6 is an important regulator of early animal development. Loss of function mutations of pax6 in a range of animals results in a reduction or complete loss of the eye, a reduction of a subset of neurons, and defects in axon growth. There are no studies focusing on the role of pax6 during development of any lophotrochozoan representative, however, expression of pax6 in the developing eye and nervous system in a number of species suggest that pax6 plays a highly conserved role in eye and nervous system formation. We investigated the functional role of pax6 during development of the marine annelid Capitella teleta. Expression of pax6 transcripts in C. teleta larvae is similar to patterns found in other animals, with distinct subdomains in the brain and ventral nerve cord as well as in the larval and adult eye. To perturb pax6 function, two different splice-blocking morpholinos were used. Larvae resulting from injections with either morpholino show a reduction of the pax6 transcript, and development of both the larval eyes and the central nervous system architecture are highly disrupted. Preliminary downstream target analysis confirms disruption in expression of some components of the retinal gene regulatory network, as well as disruption of genes involved in nervous system development. Results from this study, taken together with studies from other species, reveal an evolutionarily conserved role for pax6 in eye development, and in neural specification and development.

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