We are interested in dissecting the regulatory network underlying the generation of multiple distinct cell types from a single pluripotent precursor cell. We are using the C. elegans postembryonic mesodermal lineage, the M lineage, as a model system. The M lineage is derived from a single pluripotent cell, the M mesoblast. During hermaphrodite postembryonic development, the M cell divides to produce fourteen striated body wall muscles (BWMs), two non-muscle coelomocytes (CCs), and two sex myoblasts (SMs) that are precursors of the sixteen non-striated egg-laying muscles. Mutations in the zinc finger transcription factor SEM-4/SALL lead to the transformation of M-derived CCs and SMs to BWMs (Basson and Hortitz, 1996). We have found that sem-4 is expressed throughout the M lineage, and that overexpression of sem-4 in the M lineage can lead to the fate transformation of CCs to SMs. These results indicate that SEM-4 is both necessary and sufficient to specify the SM fate, while the level of SEM-4 is critical for proper specification of M-derived CCs. The role of SEM-4 in SM specification appears to be mediated by the SoxC protein SEM-2, which is required and sufficient for SM fate specification (Tian et al., 2011): SEM-4 is required for sem-2 expression in the SM mother and SM cells, and SEM-2 is required for sem-4-induced SM formation.
The SEM-4 protein contains seven zinc finger motifs of the C2H2 class. We have found that different sem-4 alleles that affect different zinc finger motifs exhibit different effect on CC vs. SM fate specification. These observations suggest that the distinct zinc finger motifs in SEM-4 mediate distinct functions, either having different DNA binding activities or via interacting with different co-factors, or both. Current research aims at distinguishing between these different possibilities.
References:
1) Basson M, Horvitz HR. (1996) The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein. Genes Dev. 10(15):1953-65.
2) Tian C, Shi H, Colledge C, Stern M, Waterston R, Liu J. (2011) The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm. Development. 138(6):1033-43.