Developmental Wiring of Specific Neurons Is Regulated by RET-1/Nogo-A in Caenorhabditis elegans

Genetics. 2017 Jan;205(1):295-302. doi: 10.1534/genetics.115.185322. Epub 2016 Nov 7.

Abstract

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.

Keywords: C. elegans; Nogo-A; axon guidance; ephrin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / physiology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Ephrins / metabolism
  • Membrane Proteins / genetics
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Motor Neurons / physiology
  • Neurogenesis / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Nogo Proteins / biosynthesis
  • Nogo Proteins / genetics
  • Nogo Proteins / metabolism
  • Nogo Proteins / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Ephrins
  • Membrane Proteins
  • Nogo Proteins