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.