title: Dominant negative mutations of Caenorhabditis elegans daf-7 confer a novel developmental phenotype.
abstract: BACKGROUND
  TGF-β signaling pathways are involved in the control of development in every member of the animal kingdom. As such, TGF-β ligands are widely divergent yet retain a set of core conserved features, specifically, a pre-protein cleavage site and several conserved ligand domain residues, the disruption of which produces a dominant negative phenotype.
  
  
  RESULTS
  We have extended these observations into an invertebrate system by creating a series of loss-of-function Caenorhabditis elegans daf-7 transgenes. When we tested these mutant transgenes in a daf-7/+ background, we saw a molting and excretory canal phenotype. Members of both pathways downstream of daf-4 were required for this phenotype.
  
  
  CONCLUSIONS
  Our results show that the basic mechanisms of TGF-β function are conserved across the animal kingdom. A subset of our daf-7 mutations also produced an unexpected and novel phenotype. Epistasis experiments demonstrated that both daf-3/-5 and sma-4/-9 were downstream of our mutant daf-7 transgenes, which suggests not only a role for DAF-7 in the control of molting and the development of the excretory system but also that daf-7 and dbl-1 signaling may converge downstream of their shared Type II receptor, daf-4. Our approach may unveil new roles in development for other invertebrate TGF-β ligands.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA. mxc83@psu.edu
authors.forename: Matt
authors.initials: M
authors.lastname: Crook
authors.forename: Warwick N
authors.initials: WN
authors.lastname: Grant
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009479:Neuropeptides / Q000502:physiology; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
chemical_list: D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D017931:DNA Primers; C117509:Dbl-1 protein, C elegans; D008024:Ligands; D009479:Neuropeptides; D016212:Transforming Growth Factor beta