Sexual dimorphism in the nervous system is required for sexual behavior and reproduction in many metazoan species. However, little is known of how sex determination pathways impose sex specificity on nervous system development. In C. elegans, the conserved sexual regulator MAB-3 controls several aspects of male development, including formation of V rays, male-specific sense organs required for mating. Here we show that MAB-3 promotes expression of the proneural protein LIN-32 in V ray precursors by transcriptional repression of ref-1, a member of the Hes family of neurogenic factors. Mutations in ref-1 restore lin-32::gfp expression and normal V ray development to mab-3 mutants, suggesting that ref-1 is the primary target of MAB-3 in the V ray lineage. Proteins related to MAB-3 (DM domain proteins) control sexual differentiation in diverse metazoans. We therefore suggest that regulation of Hes genes by DM domain proteins may be a general mechanism for specifying sex-specific neurons.
Bibliographical noteFunding Information:
We thank Scott Alper, Robyn Lints, Scott Emmons, Peter Okkema, David Pilgrim, Andy Fire, and Joel Rothman for strains and reagents and Doug Portman, Guillermo Marques, and Robert Herman for critical reading of the manuscript. We thank Vivian Bardwell and members of the Zarkower Lab and the University of Minnesota Center for Developmental Biology for helpful discussions. Some strains used in this work were provided by the C. elegans Genetics Center, which is funded by the NIH-NCRR. J.M.R. is supported by an NIMH predoctoral NRSA (1 F31 MH068940-01). This work was supported by a grant from the NIH (GM53099) to D.Z.