2000 East Coast Worm Meeting abstract 43
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Rutgers U
The reproductive/dauer developmental decision is controlled by environmental cues, such as food, pheromone and temperature. A TGF-beta-related pathway promotes reproductive over dauer development. Mutations in daf-7 (a TGF-beta-like ligand), daf-1and daf-4 (type I and type II receptor kinases), and daf-8 and daf-14 (Smad transcription factors) induce dauer at restrictive temperature regardless of environmental cues. The Daf-c phenotype of these mutants is suppressed by mutations in daf-3 (a Smad) or daf-5. Epistasis analysis suggests that daf-5 and daf-3 are either antagonized by this TGF-beta-related pathway or acting in a parallel pathway. The similarity of the dauer pathway to other TGF-beta pathways suggested that DAF-5 may represent a new molecule functioning in a variety of TGF-beta pathways. We have cloned daf-5 so as to study it at a molecular level.
We show that daf-5 encodes a transcription factor homologous to the human oncogene Sno. Mapping and cosmid rescue placed daf-5 in a 8 kb interval of chromosome II. We PCRed a 3.9 kb region of W01G7 from fifteen daf-5 alleles and digested the products with BstUI; we detected a polymorphism in daf-5 (sa211). This region of W01G7 encodes a Sno homologue. Sequencing of daf-5 alleles is in progess. Recently, vertebrate Sno has been shown to be capable of acting as an inhibitor of TGF-beta pathways that functions by interacting with Smad proteins. The genetic function of daf-5 suggests that the function of Sno homologues in TGF-beta pathways is broader than suggested by the vertebrate tissue culture studies, in that daf-5 is not simply acting to block signaling by the receptors.
In addition to function in the TGF-beta-related pathway, daf-5 has been shown by various groups to genetically interact with other dauer genes: daf-11 (encoding guanyl cyclase), daf-21 (encoding Hsp90), daf-2 (encoding an insulin-like ligand), and daf-28. Moreover, some daf-5 alleles have a longer life span than N2, implying daf-5 regulates life span as well as dauer formation. One allele of daf-5 does not affect life span independently; however, it further extends the life span of long-lived daf-2 mutants. These results indicate that daf-5 may control aging in parallel to the daf-2 pathway. We hope to identify the role of daf-5 in integrating information from different pathways that control dauer and other developmental events.