TGF-b-related proteins mediate a number of developmental processes. In C. elegans dauer development, DAF-7 represses dauer formation under dauer non-inducing conditions.
daf-1 and
daf-4 encode putative DAF-7 receptors.
daf-8 and
daf-3 encode homologs of Smad proteins, a recently identified family acting downstream of TGF-b receptors (D. Riddle and G. Ruvkun, pers. comm.). We cloned
daf-14 and showed that it encodes a Smad-related protein with a novel structure that lacks the conserved C-terminal domain found in all other Smad proteins. We have analyzed genetic interactions between
daf-14 and other components of the pathway. Overexpression of
daf-14 suppresses
daf-8 mutations, but not
daf-7,
daf-1, or
daf-4. This is unlikely to be due to activation of
daf-14 downstream of
daf-8 since the upstream genes
daf-7,
daf-1, and
daf-4 are not suppressed. Instead, since
daf-14 and
daf-8 encode related proteins, we think that
daf-14 is functionally substituting for
daf-8. Strong
daf-8 alleles are phenotypically weaker than strong
daf-7 alleles. To test whether partial substitution by
daf-14 is the cause of the weak
daf-8 phenotype, we compared
daf-8;
daf-14/+ to
daf-8;+/+. We found that
daf-14 dominantly enhances the Daf-c phenotype of
daf-8. Taken together, these results indicate that some degree of redundancy may exist between
daf-8 and
daf-14. Such redundancy has not been reported previously for other Smad-related proteins. We are also analyzing expression of
daf-14 using
daf-14::gfp fusions. The expression pattern is complex and dynamic throughout development. We are currently in the process of identifying the cells that express GFP. These may represent cells that respond to DAF-7 or other TGF-b-related signals during development.