Many aspects of the sexually dimorphic form and function of the developing C. elegans somatic gonad are governed by differentiated regulatory cells. In hermaphrodites, the distal tip cells (hDTCs) lead outgrowth of the two gonad arms and act as a germline niche while the anchor cell (AC) organizes vulval and uterine development. In males, the mDTCs act as the niche and the linker cell (LC) leads outgrowth of the single gonad arm. We have previously shown that each regulatory cell type expresses a unique complement of basic helix-loop-helix (bHLH) transcription factors, and proposed that a "bHLH code" specifies the fates and functions of the regulatory cells (Sallee et al. 2017). The bHLH code hypothesis posits that the inputs of sex, developmental stage, lineage, and timing leads to the expression of the appropriate bHLH complement in each prospective regulatory cell. In support of this hypothesis, we were able to reprogram the AC to assume an mDTC fate by ectopically expressing the mDTC bHLH code. We have now performed further bHLH complement manipulations and observed AC?LC and AC?hDTC cell fate transformations, and partial LC?AC transformation, consistent with the bHLH code hypothesis. To investigate sex as an input to gonadal regulatory cell specification, we are observing how regulatory cell fates are altered in sexual differentiation mutants. fkh-6(0) XO mutants have an AC (Chang et al. 2004), indicating a feminized proximal gonad, but we find that the distal regulatory cells express an mDTC marker, suggesting that other inputs specify their male identity. Finally, the different adult morphology of somatic gonads of other nematode species may reflect evolution of regulatory cell roles (Felix and Sternberg 1996). To investigate if bHLH genes control these differences, we have identified putative orthologs of the bHLH code genes in most other nematodes. Strikingly, hlh-12, which regulates migration of hDTCs and the LC in C. elegans (Tamai and Nishiwaki 2007), is not conserved in other nematodes. We plan to identify additional candidate upstream factors by searching for regulatory elements in bHLH genes that regulate their cell type-specific expression in C. elegans, and to explore bHLH expression and function in other species.

Affiliation:
- Dept of Biological Sciences, Columbia University, New York, NY