Developmental Wiring of Specific Neurons Is Regulated by RET-1/Nogo-A in Caenorhabditis elegans.
Nogo-A is a membrane-bound protein that functions to inhibit neuronal migration, adhesion, and neurite outgrowth during development. In the mature nervous system, Nogo-A stabilizes neuronal wiring to inhibit neuronal plasticity and regeneration after injury. Here, we show that RET-1, the sole Nogo-A homolog in Caenorhabditis elegans, is required to control developmental wiring of a specific subset of neurons. In ret-1 deletion mutant animals, specific ventral nerve cord axons are misguided where they fail to respect the ventral midline boundary. We found that ret-1 is expressed in multiple neurons during development, and, through mosaic analysis, showed that ret-1 controls axon guidance in a cell-autonomous manner. Finally, as in mammals, ret-1 regulates ephrin expression, and dysregulation of the ephrin ligand VAB-2 is partially responsible for the ret-1 mutant axonal defects. Together, our data present a previously unidentified function for RET-1 in the nervous system of C. elegans.
Biotech Research and Innovation Centre, University of Copenhagen, Denmark.
Nanna
N
Torpe
Biotech Research and Innovation Centre, University of Copenhagen, Denmark.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
Steffen
S
Nørgaard
Biotech Research and Innovation Centre, University of Copenhagen, Denmark.
Anette M
AM
Høye
Biotech Research and Innovation Centre, University of Copenhagen, Denmark roger.pocock@monash.edu.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
Roger
0000-0002-5515-3608
R
Pocock
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D036342:Ephrins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000070798:Nogo Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D036342:Ephrins; D008565:Membrane Proteins; D000070798:Nogo Proteins
C. elegans; Nogo-A; axon guidance; ephrin