Members of the Six4/5 family of homeobox transcription factors have been implicated in multiple human disorders, including type I mytonic dystrophy, branchio-oto-renal syndrome, and holoprosencephaly, suggesting a role for these factors in the nervous system development. Using a forward genetics approach, we identified unc-39, a C. elegans homologue of the human SIX5 gene, as a novel regulator of the development of a specific neuron, called RID. Our data support the role of unc-39 early in C. elegans development and suggest a possibility of complete absence of RID neuron in unc-39 mutants. unc-39 mutant has a similar locomotion phenotype to the RID-ablated animals, which provides further support to the hypothesis that the absence of RID contributes to the locomotion phenotype observed in the mutant. We show that unc-39 functions at multiple points in the lineage that gives rise to the RID neuron, and that its function is context-dependent.

Members of the Six4/5 family of homeobox transcription factors have been implicated in multiple human disorders, including type I mytonic dystrophy, branchio-oto-renal syndrome, and holoprosencephaly, suggesting a role for these factors in the nervous system development. Using a forward genetics approach, we identified unc-39, a C. elegans homologue of the human SIX5 gene, as a novel regulator of the development of a specific neuron, called RID. Our data support the role of unc-39 early in C. elegans development and suggest a possibility of complete absence of RID neuron in unc-39 mutants. unc-39 mutant has a similar locomotion phenotype to the RID-ablated animals, which provides further support to the hypothesis that the absence of RID contributes to the locomotion phenotype observed in the mutant. We show that unc-39 functions at multiple points in the lineage that gives rise to the RID neuron, and that its function is context-dependent.