UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans

Genes Dev. 1999 Nov 1;13(21):2774-86. doi: 10.1101/gad.13.21.2774.

Abstract

The UNC-4 homeoprotein and the Groucho-like corepressor UNC-37 specify synaptic choice in the Caenorhabditis elegans motor neuron circuit. In unc-4 mutants, VA motor neurons are miswired with inputs from interneurons normally reserved for their lineal sisters, the VB motor neurons. Here we show that UNC-4 and UNC-37 function together in VA motor neurons to repress VB-specific genes and that this activity depends on physical contact between UNC-37 and a conserved Engrailed-like repressor domain (eh1) in UNC-4. Missense mutations in the UNC-4 eh1 domain disrupt interactions between UNC-4 and UNC-37 and result in the loss of UNC-4-dependent repressor activity in vivo. A compensatory amino acid substitution in UNC-37 suppresses specific unc-4 alleles by restoring physical interactions with UNC-4 as well as UNC-4-dependent repression of VB-specific genes. We propose that repression of VB-specific genes by UNC-4 and UNC-37 is necessary for the creation of wild-type inputs to VA motor neurons. The existence of mammalian homologs of UNC-4 and UNC-37 indicates that a similar mechanism could regulate synaptic choice in the vertebrate spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Conserved Sequence
  • Gene Expression Regulation
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Homeodomain Proteins*
  • Mice
  • Molecular Sequence Data
  • Motor Neurons / physiology*
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • Nuclear Proteins*
  • Rats
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Synapses / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Homeodomain Proteins
  • Muscle Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors
  • unc-37 protein, C elegans
  • unc-4 protein, C elegans