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

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.

Download Full-text

Complex Cooperative Functions of Heparan Sulfate Proteoglycans Shape Nervous System Development in Caenorhabditis elegans

G3 Genes|Genome|Genetics ◽

10.1534/g3.114.012591 ◽

2014 ◽

Vol 4 (10) ◽

pp. 1859-1870 ◽

Cited By ~ 20

Author(s):

Carlos A. Díaz-Balzac ◽

María I. Lázaro-Peña ◽

Eillen Tecle ◽

Nathali Gomez ◽

Hannes E. Bülow

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Heparan Sulfate ◽

System Development ◽

Nervous System Development ◽

Heparan Sulfate Proteoglycans

Download Full-text

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

10.1101/481010 ◽

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.

Download Full-text

Multiple Roles of RNA Regulatory Factors in Neuronal Development and Function in C. elegans

The Oxford Handbook of Neuronal Protein Synthesis ◽

10.1093/oxfordhb/9780190686307.013.26 ◽

2020 ◽

Author(s):

Matthew G. Andrusiak ◽

Yishi Jin

Keyword(s):

Nervous System ◽

Cell Biology ◽

Molecular Mechanisms ◽

Neuronal Development ◽

Rna Binding ◽

Rna Binding Proteins ◽

Model Organism ◽

Nervous System Development ◽

Forward Genetics ◽

C Elegans

Recent evidence has highlighted the dynamic nature of mRNA regulation, particularly in the nervous system, from complex pre-mRNA processing to long-range transport and long-term storage of mature mRNAs. In accordance with the importance for mRNA-mediated regulation of nervous system development and maintenance, various mutations in RNA-binding proteins are associated with a range of human disorders. C. elegans express many RNA-binding factors that have human orthologs and perform similar biochemical functions. This chapter focuses on the research using C. elegans to dissect molecular mechanisms involving mRNA-mediated pathways. It highlights the key approaches and findings that integrate genetic and genomic studies in the nervous system. The analyses of genetic mutants, primarily using forward genetics, offer functional insights for genes important for neuronal development, synaptic transmission, and neuronal repair. In combination with single-neuron cell biology and cell-type genomics, the knowledge learned from this model organism has continued to lead to ground-breaking discoveries.

Download Full-text

ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401126 ◽

2020 ◽

Vol 10 (6) ◽

pp. 1949-1962 ◽

Cited By ~ 1

Author(s):

Elyse L. Christensen ◽

Alexandra Beasley ◽

Jessica Radchuk ◽

Zachery E. Mielko ◽

Elicia Preston ◽

...

Keyword(s):

Nervous System ◽

Transcription Factors ◽

Caenorhabditis Elegans ◽

Cell Fate ◽

Neural Development ◽

System Development ◽

Neuronal Cell ◽

Nervous System Development ◽

Link Type ◽

Neuroblast Migration

Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis.

Download Full-text

No pun intended: future directions in invertebrate glial cell migration studies

Neuron Glia Biology ◽

10.1017/s1740925x07000634 ◽

2007 ◽

Vol 3 (1) ◽

pp. 45-54 ◽

Cited By ~ 4

Author(s):

Patrick Cafferty ◽

Vanessa J. Auld

Keyword(s):

Nervous System ◽

Cell Migration ◽

Glial Cell ◽

Glial Cells ◽

Molecular Mechanisms ◽

System Development ◽

Fruit Fly ◽

Nervous System Development ◽

Wide Range ◽

And Function

AbstractGlial cells play a wide range of essential roles in both nervous system development and function and has been reviewed recently (Parker and Auld, 2006). Glia provide an insulating sheath, either form or direct the formation of the blood–brain barrier, contribute to ion and metabolite homeostasis and provide guidance cues. Glial function often depends on the ability of glial cells to migrate toward specific locations during nervous system development. Work in nervous system development in insects, in particular in the fruit fly Drosophila melanogaster and the tobacco hornworm Manduca sexta, has provided significant insight into the roles of glia, although the molecular mechanisms underlying glial cell migration are being determined only now. Indeed, many of the processes and mechanisms discovered in these simpler systems have direct parallels in the development of vertebrate nervous systems. In this review, we first examine the developmental contexts in which invertebrate glial cell migration has been observed, we next discuss the characterized molecules required for proper glial cell migration, and we finally discuss future goals to be addressed in the study of glial cell development.

Download Full-text

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

10.32920/ryerson.14644275.v1 ◽

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.

Download Full-text

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

10.1101/022756 ◽

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.

Download Full-text

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

10.1101/148080 ◽

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.

Download Full-text

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

eLife ◽

10.7554/elife.29257 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 19

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.

Download Full-text