Dominant unc-37 mutations suppress the movement defect of a homeodomain mutation in unc-4, a neural specificity gene in Caenorhabditis elegans.
The unc-4 gene of Caenorhabditis elegans encodes a homeodomain protein that defines synaptic input to ventral cord motor neurons. unc-4 mutants are unable to crawl backward because VA motor neurons are miswired with synaptic connections normally reserved for their sister cells, the VB motor neurons. These changes in connectivity are not accompanied by any visible effects upon neuronal morphology, which suggests that unc-4 regulates synaptic specificity but not axonal guidance or outgrowth. In an effort to identify other genes in the unc-4 pathway, we have devised a selection scheme for rare mutations that suppress the Unc-4 phenotype. We have isolated four, dominant, extragenic, allele-specific suppressors of unc-4(e2322ts), a temperature sensitive allele with a point mutation in the unc-4 homeodomain. Our data indicate that these suppressors are gain-of-function mutations in the previously identified unc-37 gene. We show that the loss-of-function mutation unc-37(e262) phenocopies the Unc-4 movement defect but does not prevent unc-4 expression or alter VA motor neuron morphology. These findings suggest that unc-37 functions with unc-4 to specify synaptic input to the VA motor neurons. We propose that unc-37 may be regulated by unc-4. Alternatively, unc-37 may encode a gene product that interacts with the unc-4 homeodomain.
Miller
D M
DM
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710-3011.
Niemeyer
C J
CJ
Chitkara
P
P
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D005260:Female; D005799:Genes, Dominant; D017238:Genes, Helminth; D005801:Genes, Homeobox; D016153:Genes, Suppressor; D008040:Genetic Linkage; D015801:Helminth Proteins / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology; D009068:Movement / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009420:Nervous System / Q000254:growth & development; D009424:Nervous System Physiological Phenomena; D010641:Phenotype; D013569:Synapses / Q000502:physiology
D015801:Helminth Proteins; D009419:Nerve Tissue Proteins