Inhibition of Caenorhabditis elegans vulval induction by gap-1 and by let-23 receptor tyrosine kinase.
During induction of the Caenorhabditis elegans hermaphrodite vulva, a signal from the anchor cell activates the LET-23 epidermal growth factor receptor (EGFR)/LET-60 Ras/MPK-1 MAP kinase signaling pathway in the vulval precursor cells. We have characterized two mechanisms that limit the extent of vulval induction. First, we found that gap-1 may directly inhibit the LET-60 Ras signaling pathway. We identified the gap-1 gene in a genetic screen for inhibitors of vulval induction. gap-1 is predicted to encode a protein similar to GTPase-activating proteins that likely functions to inhibit the signaling activity of LET-60 Ras. A loss-of-function mutation in gap-1 suppresses the vulvaless phenotype of mutations in the let-60 ras signaling pathway, but a gap-1 single mutant does not exhibit excess vulval induction. Second, we found that let-23 EGFR prevents vulval induction in a cell-nonautonomous manner, in addition to its cell-autonomous role in activating the let-60 ras/mpk-1 signaling pathway. Using genetic mosaic analysis, we show that let-23 activity in the vulval precursor cell closest to the anchor cell (P6.p) prevents induction of vulval precursor cells further away from the anchor cell (P3.p, P4.p, and P8.p). This result suggests that LET-23 in proximal vulval precursor cells might bind and sequester the inductive signal LIN-3 EGF, thereby preventing diffusion of the inductive signal to distal vulval precursor cells.
Hajnal
A
A
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305 USA.
Whitfield
C W
CW
Kim
S K
SK
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004330:Drosophila; D004625:Embryo, Nonmammalian / Q000502:physiology; D004627:Embryonic Induction; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014844:Vulva / Q000196:embryology; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins
D029742:Caenorhabditis elegans Proteins; C108739:GAP-1 protein, C elegans; D015801:Helminth Proteins; D020703:ras GTPase-Activating Proteins; C066646:let-60 protein, C elegans; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C085873:let-23 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans; D018631:ras Proteins