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UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans
- Source :
- Genes & Development. 13:2774-2786
- Publication Year :
- 1999
- Publisher :
- Cold Spring Harbor Laboratory, 1999.
-
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.
- Subjects :
- Transcription, Genetic
Molecular Sequence Data
Mutant
Muscle Proteins
Repressor
macromolecular substances
Biology
Mice
Genetics
medicine
Animals
Missense mutation
Amino Acid Sequence
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Psychological repression
Gene
Conserved Sequence
Homeodomain Proteins
Motor Neurons
Binding Sites
Sequence Homology, Amino Acid
fungi
Nuclear Proteins
Helminth Proteins
Motor neuron
biology.organism_classification
Rats
Cell biology
Repressor Proteins
medicine.anatomical_structure
Amino Acid Substitution
Gene Expression Regulation
nervous system
Synapses
Corepressor
Research Paper
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 08909369
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Genes & Development
- Accession number :
- edsair.doi.dedup.....43247a7ed0059083841814bd49154f9d