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PMID: 10557206 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Genes & development ·Vol. 13 ·No. 21 ·1999-11-01 ·Pages 2774-86

Winnier AR, Meir JY, Ross JM, Tavernarakis N, Driscoll M, Ishihara T, Katsura I, Miller DM

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.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Animals Binding Sites Caenorhabditis elegans/genetics,physiology Caenorhabditis elegans Proteins Conserved Sequence Gene Expression Regulation Helminth Proteins/genetics,physiology Homeodomain Proteins Mice Molecular Sequence Data Motor Neurons/physiology Muscle Proteins/genetics,physiology Nuclear Proteins Rats Repressor Proteins/genetics,physiology Sequence Homology, Amino Acid Synapses/physiology Transcription Factors/genetics,physiology Transcription, Genetic
Chemicals
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
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Winnier A R
Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Meir J Y
Ross J M
Tavernarakis N
Driscoll M
Ishihara T
Katsura I
Miller D M
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.21.2774
Published
1999-11-01
Pages
2774-86
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317130
Subset
IM
Grants
NIMH NIH HHS · F31 MH011831 · United States
NINDS NIH HHS · R01 NS026115 · United States
NIMH NIH HHS · MH-11831 · United States
NCI NIH HHS · 1P30 CA68485 · United States
NINDS NIH HHS · NS 26115 · United States
NCI NIH HHS · P30 CA068485 · United States
External Links
PubMed source DOI: 10.1101/gad.13.21.2774 PMC Full Text View journal details
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