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.

scholarly journals The development of early pioneer neurons in the annelid Malacoceros fuliginosus

2020 ◽  
Author(s):  
Suman Kumar ◽  
Sharat Chandra Tumu ◽  
Conrad Helm ◽  
Harald Hausen
Keyword(s):  
Nervous System ◽  
Synapse Formation ◽  
System Development ◽  
Posterior Pole ◽  
Nervous System Development ◽  
Whole Body ◽  
Neural Patterning ◽  
Neuronal Progenitors ◽  
Pioneer Neurons ◽  
Clonal Origin

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 first steps of nervous system development in the annelid Malacoceros fuliginosus . Results Here, we performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 hours postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d 221 ), which after 7 cleavages starts expressing Neurogenin , Achaete-Scute and NeuroD . Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. The specification of the relevant neurons starts very early and we suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

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 The development of early pioneer neurons in the annelid Malacoceros fuliginosus

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Suman Kumar ◽  
Sharat Chandra Tumu ◽  
Conrad Helm ◽  
Harald Hausen
Keyword(s):  
Nervous System ◽  
Synapse Formation ◽  
System Development ◽  
Posterior Pole ◽  
Nervous System Development ◽  
Whole Body ◽  
Neural Patterning ◽  
Neuronal Progenitors ◽  
Pioneer Neurons ◽  
Clonal Origin

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 first steps of nervous system development in the annelid Malacoceros fuliginosus. Results We performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 h postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d221), which after 7 cleavages starts expressing Neurogenin, Acheate-Scute and NeuroD. Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. We suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

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 The Role of Chondroitin Sulfate Proteoglycans in Nervous System Development

2020 ◽  
Vol 69 (1) ◽  
pp. 61-80 ◽  
Author(s):  
Caitlin P. Mencio ◽  
Rowan K. Hussein ◽  
Panpan Yu ◽  
Herbert M. Geller
Keyword(s):  
Nervous System ◽  
Chondroitin Sulfate ◽  
Neural Development ◽  
Synapse Formation ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Chondroitin Sulfate Proteoglycans ◽  
Cell Proliferation And Differentiation

The orderly development of the nervous system is characterized by phases of cell proliferation and differentiation, neural migration, axonal outgrowth and synapse formation, and stabilization. Each of these processes is a result of the modulation of genetic programs by extracellular cues. In particular, chondroitin sulfate proteoglycans (CSPGs) have been found to be involved in almost every aspect of this well-orchestrated yet delicate process. The evidence of their involvement is complex, often contradictory, and lacking in mechanistic clarity; however, it remains obvious that CSPGs are key cogs in building a functional brain. This review focuses on current knowledge of the role of CSPGs in each of the major stages of neural development with emphasis on areas requiring further investigation:

scholarly journals Role of miRNA-mRNA Interaction in Neural Stem Cell Differentiation of Induced Pluripotent Stem Cells

2020 ◽  
Vol 21 (19) ◽  
pp. 6980
Author(s):  
Satish Kumar ◽  
Joanne E. Curran ◽  
Erica DeLeon ◽  
Ana C. Leandro ◽  
Tom E. Howard ◽  
...  
Keyword(s):  
Nervous System ◽  
Synapse Formation ◽  
System Development ◽  
Target Prediction ◽  
Stem Cell Differentiation ◽  
Nervous System Development ◽  
P Value ◽  
Protein Coding ◽  
Human Ipscs

miRNA regulates the expression of protein coding genes and plays a regulatory role in human development and disease. The human iPSCs and their differentiated progenies provide a unique opportunity to identify these miRNA-mediated regulatory mechanisms. To identify miRNA–mRNA regulatory interactions in human nervous system development, well characterized NSCs were differentiated from six validated iPSC lines and analyzed for differentially expressed (DE) miRNome and transcriptome by RNA sequencing. Following the criteria, moderated t statistics, FDR-corrected p-value ≤ 0.05 and fold change—absolute (FC-abs) ≥2.0, 51 miRNAs and 4033 mRNAs were found to be significantly DE between iPSCs and NSCs. The miRNA target prediction analysis identified 513 interactions between 30 miRNA families (mapped to 51 DE miRNAs) and 456 DE mRNAs that were paradoxically oppositely expressed. These 513 interactions were highly enriched in nervous system development functions (154 mRNAs; FDR-adjusted p-value range: 8.06 × 10−15–1.44 × 10−4). Furthermore, we have shown that the upregulated miR-10a-5p, miR-30c-5p, miR23-3p, miR130a-3p and miR-17-5p miRNA families were predicted to down-regulate several genes associated with the differentiation of neurons, neurite outgrowth and synapse formation, suggesting their role in promoting the self-renewal of undifferentiated NSCs. This study also provides a comprehensive characterization of iPSC-generated NSCs as dorsal neuroepithelium, important for their potential use in in vitro modeling of human brain development and disease.

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