lin-1 has both positive and negative functions in specifying multiple cell fates induced by Ras/MAP kinase signaling in C. elegans.
lin-1 encodes an ETS domain transcription factor that functions downstream of a Ras/MAP kinase pathway mediating induction of the 1 degrees cell fate during vulval development in the C. elegans hermaphrodite. Mutants lacking lin-1 activity display a phenotype similar to that caused by mutations that constitutively activate let-60 Ras consistent with a model in which lin-1 is a repressor of the 1 degree fate whose activity is inhibited by phosphorylation by MPK-1 MAP kinase. Here, we show that, contrary the current model, lin-1 is required positively for the proper expression of several genes regulated by the pathway in cells adopting the 1 degrees cell fate. We show that the positive requirement for lin-1 is downstream of let-60 Ras and mpk-1 MAP kinase, and that it has a focus in the vulval precursor cells themselves. lin-1 alleles encoding proteins lacking a docking site for MPK-1 MAP kinase are defective in the positive function. We also show that lin-1 apparently has both positive and negative functions during the specification of the fates of other cells in the worm requiring Ras/MAP kinase signaling.
Tiensuu
Teresa
T
Umeå Center for Molecular Pathogenesis, Umeå University, SE-901 87 Umeå, Sweden.
Larsen
Morten Krog
MK
Vernersson
Emma
E
Tuck
Simon
S
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012734:Disorders of Sex Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D049452:Green Fluorescent Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014844:Vulva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C105157:Egl-17 protein, C elegans; D036341:Intercellular Signaling Peptides and Proteins; C097533:Lin-1 protein, C elegans; D011994:Recombinant Proteins; D014157:Transcription Factors; C081464:lin-31 protein, C elegans; C066646:let-60 protein, C elegans; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans; D018631:ras Proteins