SEM-2/SoxC regulates multiple aspects of C. elegans postembryonic mesoderm development

Development of multicellular organisms requires well-orchestrated interplay between cell-intrinsic transcription factors and cell-cell signaling. One set of highly conserved transcription factors that plays diverse roles in development is the SoxC group. C. elegans contains a sole SoxC protein, SEM-2. SEM-2 is essential for embryonic development, and for specifying the sex myoblast (SM) fate in the postembryonic mesoderm, the M lineage. We have identified a novel partial loss-of-function sem-2 allele that has a proline to serine change in the C-terminal tail of the highly conserved DNA-binding domain. Detailed analyses of mutant animals harboring this point mutation uncovered new functions of SEM-2 in the M lineage. First, SEM-2 functions antagonistically with LET-381, the sole C. elegans FoxF/C forkhead transcription factor, to regulate dorsoventral patterning of the M lineage. Second, in addition to specifying the SM fate, SEM-2 is essential for the proliferation and diversification of the SM lineage. Finally, SEM-2 appears to directly regulate the expression of hlh-8, which encodes a basic helix-loop-helix Twist transcription factor and plays critical roles in proper patterning of the M lineage. Our data, along with previous studies, suggest an evolutionarily conserved relationship between SoxC and Twist proteins. Furthermore, our work identified new interactions in the gene regulatory network (GRN) underlying C. elegans postembryonic development and adds to the general understanding of the structure-function relationship of SoxC proteins. AUTHOR SUMMARYSoxC transcription factors play important roles in metazoan development. Abnormal expression or function of SoxC factors has been linked to a variety of developmental disorders and cancers. It is therefore critical to understand the functions of SoxC proteins in vivo. C. elegans has a single SoxC transcription factor, SEM-2, that is known to regulate a fate decision between a proliferative progenitor cell vs. a terminally differentiated cell during postembryonic mesoderm development. In this study, we report new functions of SEM-2 in postembryonic mesoderm development via our studies of a partial loss-of-function allele of sem-2. Our work uncovers new regulatory relationships between SEM-2/SoxC and the FoxF/C transcription factor LET-381, and between SEM-2/SoxC and the C. elegans Twist ortholog HLH-8. Our findings suggest that the SoxC-Twist axis, including the downstream targets of Twist, represents an evolutionarily conserved regulatory cassette important in metazoan development.