The Role Of The Daf 8 Gene In Caenorhabditis Elegans Dauer Larva Development PDF Download

When starved and overcrowded, the free-living soil nematode C. elegans can form a developmentally arrested dispersal stage called the dauer larva. This process is partially mediated by TGF-$\beta$-induced signalling. Mutations in the daf-8 gene result in constitutive dauer larva formation (Daf-c), reduced fecundity, and some embryonic and larval lethality. This gene has been cloned by transposon tagging. A region flanking a transposon insertion in daf-8 hybridizes to two overlapping cosmids. Sequence analysis of cosmid subclones identifies a Smad family protein shown by mutation site analysis to be encoded by daf-8. Mutational and phenotypic analyses have defined amino acids 389-415 as a region of the protein important for embryonic and larval viability. A cosmid fragment used to probe a developmental northern hybridized to 1.3 kb and 1.6 kb transcripts. The smaller transcript is expressed most strongly in L1 and dauer larvae, two stages in which major developmental decisions are made. The daf-7 gene encodes a TGF-$\beta$ ligand that putatively binds the DAF-4/DAF-1 receptor complex, regulating dauer larva formation. All daf-1, daf-4 and daf-7 mutants are Daf-c. Additionally, daf-4 mutants have phenotypes not shared in common with daf-7 mutants. Another C. elegans TGF-$\beta$ ligand, CeBMP, identified by degenerate PCR, may be involved in regulation of some of the daf-4-specific phenotypes. Since TGF-$\beta$ ligands function as dimers, CeBMP may dimerize with DAF-7 to regulate dauer larva formation. I propose a model by which dauer larva formation is regulated by DAF-7/CeBMP binding to the DAF-4 and DAF-1 receptors. DAF-1 phosphorylates DAF-8 which along with DAF-14, antagonizes the activity of DAF-3 to initiate growth and prevent dauer larva formation.