Differences between female and male brains have been observed in species across the animal kingdom. In C. elegans, the defined connectomes for both male and hermaphrodite animals give neuron-specific resolution of highly sexually dimorphic synaptic connectivity (1), but the genetic factors underlying this dimorphic connectivity are largely unknown. Genes of the Doublesex/mab domain (dmd) family exist in all animal phyla and have been broadly implicated downstream of sex determination pathways. One of the few highly conserved members of this family in C. elegans,
dmd-4, is expressed non-dimorphically in the sex-shared phasmid sensory neurons of juvenile animals, with expression becoming sexually dimorphic in adulthood. In adult animals, the phasmid neurons make sexually dimorphic synaptic connections onto downstream sex-shared interneurons, and we have shown that these synaptic connections facilitate sexually dimorphic behavioral outputs (2). However, the genes underlying these cellular dimorphisms have not been described. Although there is evidence that dimorphic expression of other dmd genes in C. elegans is established transcriptionally by the
tra-1/Gli transcription factor (3), we found that
dmd-4 is transcribed in both sexes and dimorphic adult expression is established post-translationally via a highly conserved domain, the DMA domain, which we find binds ubiquitin both in C. elegans and in humans. When fused to GFP alone and expressed throughout the entire nervous system, the DMA domain is sufficient to confer protein degradation with temporal, but with no spatial or sexual specificity. Our findings suggest the existence of a novel regulatory mechanism acting in the phasmid neurons to establish sexually dimorphic connectivity and behavior. We have generated a tissue-specific knockout allele to pursue this potential role of
dmd-4 in establishing neuron identity, sexually dimorphic synaptic connectivity, and downstream behavioral output. 1. Jarrell TA, Wang Y, Bloniarz AE, Brittin CA, Xu M, Thomson JN, Albertson DG, Hall DH, Emmons SW. 2012. Science 337, 437-444. 2. Oren-Suissa M, Bayer EA, Hobert O. 2016. Nature 533, 206-211. 3. Mason DA, Rabinowitz JS, Portman DS. 2008. Development 135, 2373-2382