scholarly journals Analysis of the ENU-3 protein family in nervous system development in C. elegans.

2021 ◽  
Author(s):  
Roxana O. Florica
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
The Novel ◽  
Intracellular Membrane ◽  
C Elegans ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Dependent Pathway ◽  
Novel Protein

During the development of the nervous system, neurons are guided to their final targets by several well-known guidance cues. In Caenorhabditis elegans the expression of the UNC-6/Netrin guidance cue along the ventral cord attracts axons that express UNC-40, while repulsing axons that express both the UNC-5 and UNC-40 receptors. Lack of both UNC-40 and the novel protein ENU-3 enhanced the ventral guidance defects of the AVM and PVM (Yee et al., 2014). This suggests that ENU-3 functions in an UNC-6 dependent pathway parallel to UNC-40 in controlling migrations towards the ventral nerve cord. Mutations in all proteins of the ENU-3 family also enhance the motor neuron axon outgrowth defects of strains lacking UNC-6 or the UNC-5 receptor, thus they function in a parallel unknown pathway (Yee et al., 2011). Expression analyses in HeLa cells have determined that ENU-3 and one of its paralogs, C38D4.1 localize to the nuclear membrane/ER while another of its paralogs, K01G5.3 is an intracellular membrane-associated protein.

scholarly journals Analysis of the ENU-3 protein family in nervous system development in C. elegans.

2021 ◽  
Author(s):  
Roxana O. Florica
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
The Novel ◽  
Intracellular Membrane ◽  
C Elegans ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Dependent Pathway ◽  
Novel Protein

During the development of the nervous system, neurons are guided to their final targets by several well-known guidance cues. In Caenorhabditis elegans the expression of the UNC-6/Netrin guidance cue along the ventral cord attracts axons that express UNC-40, while repulsing axons that express both the UNC-5 and UNC-40 receptors. Lack of both UNC-40 and the novel protein ENU-3 enhanced the ventral guidance defects of the AVM and PVM (Yee et al., 2014). This suggests that ENU-3 functions in an UNC-6 dependent pathway parallel to UNC-40 in controlling migrations towards the ventral nerve cord. Mutations in all proteins of the ENU-3 family also enhance the motor neuron axon outgrowth defects of strains lacking UNC-6 or the UNC-5 receptor, thus they function in a parallel unknown pathway (Yee et al., 2011). Expression analyses in HeLa cells have determined that ENU-3 and one of its paralogs, C38D4.1 localize to the nuclear membrane/ER while another of its paralogs, K01G5.3 is an intracellular membrane-associated protein.

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 sli is required for proper morphology and migration of sensory neurons in the Drosophila PNS

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Madison Gonsior ◽  
Afshan Ismat
Keyword(s):  
Nervous System ◽  
Sensory Neurons ◽  
Glial Cells ◽  
System Development ◽  
Nervous System Development ◽  
Final Position ◽  
Neuron Development ◽  
Guidance Cues ◽  
And Migration

Abstract Neurons and glial cells coordinate with each other in many different aspects of nervous system development. Both types of cells are receiving multiple guidance cues to guide the neurons and glial cells to their proper final position. The lateral chordotonal organs (lch5) of the Drosophila peripheral nervous system (PNS) are composed of five sensory neurons surrounded by four different glial cells, scolopale cells, cap cells, attachment cells and ligament cells. During embryogenesis, the lch5 neurons go through a rotation and ventral migration to reach their final position in the lateral region of the abdomen. We show here that the extracellular ligand sli is required for the proper ventral migration and morphology of the lch5 neurons. We further show that mutations in the Sli receptors Robo and Robo2 also display similar defects as loss of sli, suggesting a role for Slit-Robo signaling in lch5 migration and positioning. Additionally, we demonstrate that the scolopale, cap and attachment cells follow the mis-migrated lch5 neurons in sli mutants, while the ventral stretching of the ligament cells seems to be independent of the lch5 neurons. This study sheds light on the role of Slit-Robo signaling in sensory neuron development.

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 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 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 TheC. elegansephrin EFN-4 functions non-cell autonomously with heparan sulfate proteoglycans to promote axon outgrowth and branching

2015 ◽  
Author(s):  
Alicia A Schwieterman ◽  
Alyse N Steves ◽  
Vivian Yee ◽  
Cory J Donelson ◽  
Aaron Pital ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurite Outgrowth ◽  
Motor Neurons ◽  
System Development ◽  
Nervous System Development ◽  
The Body ◽  
Tissue Type ◽  
Eph Receptors ◽  
C Elegans ◽  
Core Proteins

The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for theCaenorhabditis elegansephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in aC. elegansmodel of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body wall muscle, and in parallel with HS biosynthesis genes and HSPG core proteins, which function cell autonomously in the AIY neurons. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system.

scholarly journals Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans

2017 ◽  
Author(s):  
Byunghyuk Kim ◽  
Scott W. Emmons
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Sensory Neuron ◽  
Protein Interactions ◽  
Synapse Formation ◽  
System Development ◽  
Nervous System Development ◽  
Surface Proteins ◽  
C Elegans ◽  
Nervous System Function

ABSTRACTNervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

scholarly journals Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Byunghyuk Kim ◽  
Scott W Emmons
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Sensory Neuron ◽  
Protein Interactions ◽  
Synapse Formation ◽  
System Development ◽  
Nervous System Development ◽  
Surface Proteins ◽  
C Elegans ◽  
Nervous System Function

Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

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