Worm Breeder's Gazette 13(4): 62 (October 1, 1994)
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.
Division of Biological Sciences, University of Missouri, Columbia, MO 65211 Dauer larva formation involves a complex signaling pathway initiated by chemosensation in the amphid neurons, and ending in changes in gene expression throughout the organism. Several genes, daf-1, daf-4 and daf-7, which promote non-dauer development, encode cell-surface receptors or ligands of the TGF-beta superfamily. Members of this superfamily are involved in many aspects of growth and development in mammals, frogs and flies - e.g. body plan specification in early embryogenesis, control of limb, bone, cartilage, neural tube and sexual organ formation, immune and endocrine functions and so on. How signals are transduced from TGF-beta-like receptors to the nucleus is unknown. By contrast, the sem-5/let-60/lin-45/mpk-1 or sur-1 vulval induction pathway involved in signal transduction from the EGF-type let-23 tyrosine kinase receptor is well characterized (1). We wanted to know whether components of the vulval induction pathway are involved in signal transduction from the daf-4 receptor (2). Double mutants were made using a weak daf-4 mutation, m592, and sem-5(n1779), let-60(s59lf), let-60(n1046gf), lin-45(sy96) and mpk-1(n2521) (thanks to Paul Sternberg and Stuart Kim for sending strains). At 22.5oC, m592 causes a small adult body size (Sma) phenotype, and at 25oC forms >90% dauer larvae (Daf-c). Double mutants were tested for enhancement or suppression of Daf-c or Sma. None of the let-23 pathway mutants had any substantial effect on the Daf-c phenotype. However, let-60(gf) did enhance the Sma phenotype, perhaps by activating a function antagonistic to daf-4 in its body size-determining capacity. let-60(gf) does not have any detectable effect on the daf-4(m592) male tail defects (Scott Baird, personal communication). These results suggest that TGF-beta receptors transduce signals to the nucleus via a distinct pathway of signaling components. Given the conservation of the EGF signaling pathway between yeast, Caenorhabditis, Drosophila and mammals, this result may prove to be general to receptors for TGF-beta family ligands. We have not yet studied more severe alleles of sem-5 or mpk-1/sur-1, or a dominant negative mutant allele of let-60. Interaction between daf-4(m592) and unc-101(m1) was also examined. unc-101 mutations suppress a hypomorphic allele of let-23, possibly the result of abnormal trafficking of the LET-23 receptor causing an an increase in its effective activity (3). Here, however, some enhancement of Daf-c was observed. This could reflect a functional property of the daf-4(m592) receptor, or, as is more likely, a synergistic effect on the function of the neurons which control dauer development since unc-101(m1) causes ciliary abnormalities in amphid sensory neurons (Hall and Hedgecock, WBG 11 -1: 56). (1) Sternberg, Ann. Rev. of Genet. 27 497-520, 1993. (2) Estevez et al., Nature 365 644-649, 1993. (3) Lee et al., Genes and Dev. 8 60-73, 1994.