E and MS, though sisters, undergo highly different developmental programs. While the E cell gives rise only to gut (endoderm), MS produces primarily mesodermal tissue, including posterior pharynx and somatic gonad. The maternal
skn-1 gene is required for EMS fate: in
skn-1 mutants, both E and MS can adopt a C-like fate.
end-1 and
end-3 encode redundant GATA factors that appear to act downstream of SKN-1 in the E lineage to promote endoderm development. These genes are repressed in the MS lineage by maternal POP-1. Until recently, no zygotic factors were known that directly act to specify MS fate. We have found that an
end-3 neomorphic mutation (
zu247 ) identified by Russell Hill and Jim Priess causes E to adopt an MS fate and alters a single residue in the zinc finger of END-3. This observation suggested that the altered END-3 protein might function like an MS-promoting GATA factor. Indeed, we identified a pair of redundant GATA factors, MED-1 and MED-2, that specify MS.
med-1 and
med-2 are on separate linkage groups and are 98% identical. RNAi of
med-1 and
med-2 results in embryos lacking the MSaa and MSpa-derived posterior pharynx, and blocks expression of MSap-specific
lag-2 . This defect in MS specification is accompanied by ectopic expression of
vab-7 , a C-lineage-specific marker, suggesting that MS adopts a C fate. In addition, ~1/3 of mutant embryos also lack gut, suggesting a role in E specification. Reporter fusions of both med genes show SKN-1-dependent expression in the early E and MS lineages. However, ectopically expressed
med-1 appears to promote only ectopic MS fate, while suppressing E fate. This suggests that the med genes act in parallel with the Wnt pathway in E specification, promoting E fate only when both the med and end genes are expressed. We postulate that MS fate is specified by the med genes, driven by SKN-1, coupled with the repression of the end genes. In E, the Wnt signal activates the end genes, and the med / end combination promotes E fate. These findings also indicate a remarkable similarity in the mechanisms that specify E and MS: both blastomeres require redundant pairs of GATA factors that dictate their identities in a cell that otherwise adopts a C-like cell fate.