Our lab is studying mesodermal development using the C. elegans postembryonic lineage, the M lineage, as a model system. The M lineage gives rise to a variety of mesodermal cell types. In particular, the dorsal daughter of M (Md) produces two coelomocytes, while the ventral daughter Mv produces two sex myoblasts. The mechanisms regulating this dorsal-ventral asymmetry are not well understood. We have identified SMA-9 as one of the factors regulating this asymmetry. Mutations in
sma-9 resulted in the transformation of the dorsal fates to the ventral fates in the M lineage.
sma-9 encodes a nuclear localized C2H2 zinc finger protein that is homologous to the Drosophila protein Schnurri. Mutations in
sma-9 also lead to small body sizes and male tail patterning defects (Liang et al., 2003). In order to understand how SMA-9 functions in the M lineage, we carried out a mutagenesis screen and isolated 7 suppressor mutations that specifically suppressed the M lineage defects of
sma-9(
cc604). One of our suppressor mutations
jj3 is an allele of
sma-3, which encodes a regulatory Smad of the DBL-1/TGF-beta signaling pathway.
sma-3 mutations caused no M lineage defects on their own, yet they completely suppressed the M lineage phenotypes, but not the small body size, of
sma-9 mutants. We further showed that mutations in genes encoding the DBL-1 ligand, the DAF-4 and SMA-6 receptors and the SMA-2 and SMA-4 Smads proteins all suppressed the M lineage defects of
sma-9 mutants without suppressing their small body size phenotype. Since mutations in all the above TGF-beta pathway components caused no M lineage defects, their interactions with
sma-9 have allowed us to uncover a novel role of the TGF-beta signaling pathway in patterning the postembryonic mesoderm. We showed that this genetic interaction between
sma-9 and the TGF-beta pathway is specific, since mutations in the Wnt signaling pathway did not suppress the M lineage phenotypes of
sma-9 mutants. The Drosophila SMA-9 homolog Schnurri has been shown to act as a transcriptional repressor (Marty et al., 2000). We therefore propose that in the C. elegans postembryonic mesoderm SMA-9 functions in parallel to the TGF-beta signaling pathway to antagonize its function. We are currently further testing this hypothesis and addressing possible targets of
sma-9 in the M lineage.