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

Winnier AR, Meir JY, Ross JM, Tavernarakis N, Driscoll M, Ishihara T, Katsura I, Miller DM
Genes Dev. 1999 13 (21): 2774-86

PMID: 10557206 · PMCID: PMC317130 · DOI:10.1101/gad.13.21.2774

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 (21)

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

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