Notch Inhibition of RAS Signaling Through MAP Kinase Phosphatase LIP-1 During C. elegans Vulval Development

During Caenorhabditis elegans vulval development, a signal from the anchor cell stimulates the RTK/RAS/MAPK (receptor tyrosine kinase/RAS/mitogen-activated protein kinase) signaling pathway in the closest vulval precursor cell P6.p to induce the primary fate. A lateral signal from P6.p then activates the Notch signaling pathway in the neighboring cells P5.p and P7.p to prevent them from adopting the primary fate and to specify the secondary fate. The MAP kinase phosphatase LIP-1 mediates this lateral inhibition of the primary fate. LIN-12/NOTCH up-regulateslip-1 transcription in P5.p and P7.p where LIP-1 inactivates the MAP kinase to inhibit primary fate specification. LIP-1 thus links the two signaling pathways to generate a pattern.

[1]  Stuart K. Kim,et al.  MAP Kinase Signaling Specificity Mediated by the LIN-1 Ets/LIN-31 WH Transcription Factor Complex during C. elegans Vulval Induction , 1998, Cell.

[2]  H. Horvitz,et al.  The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways. , 1989, Genetics.

[3]  S. Hayashi,et al.  Interplay of Notch and FGF signaling restricts cell fate and MAPK activation in the Drosophila trachea. , 1999, Development.

[4]  S. Artavanis-Tsakonas,et al.  Notch Signaling : Cell Fate Control and Signal Integration in Development , 1999 .

[5]  H. Horvitz,et al.  C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains , 1992, Nature.

[6]  H. Horvitz,et al.  Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction , 1990, Nature.

[7]  Thomas R Clandinin,et al.  Different Levels of the C. elegans growth factor LIN-3 promote distinct vulval precursor fates , 1995, Cell.

[8]  S. K. Kim,et al.  Inhibition of Caenorhabditis elegans vulval induction by gap-1 and by let-23 receptor tyrosine kinase. , 1997, Genes & development.

[9]  H. Horvitz,et al.  A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans. , 1994, Genes & development.

[10]  Stuart K. Kim,et al.  Genetic analysis of the Caenorhabditis elegans MAP kinase gene mpk-1. , 1998, Genetics.

[11]  A. Ashworth,et al.  Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and Raf. , 1995, Methods in enzymology.

[12]  Paul W. Sternberg,et al.  Lateral inhibition during vulval induction in Caenorhabditis elegans , 1988, Nature.

[13]  R. Burdine,et al.  EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans. , 1998, Development.

[14]  P. Sternberg,et al.  Mutations in the Caenorhabditis elegans let‐23 EGFR‐like gene define elements important for cell‐type specificity and function. , 1994, The EMBO journal.

[15]  M. Bosenberg,et al.  lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). , 1996, Development.

[16]  M. Camps,et al.  Dual specificity phosphatases: a gene family for control of MAP kinase function , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  I. Greenwald,et al.  lin-25, a gene required for vulval induction in Caenorhabditis elegans. , 1995, Genes & development.

[18]  V. Ambros,et al.  Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells. , 1999, Development.

[19]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway. , 1995, Genes & development.

[20]  Stuart K. Kim,et al.  LET-23 Receptor Localization by the Cell Junction Protein LIN-7 during C. elegans Vulval Induction , 1996, Cell.

[21]  Min Han,et al.  Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation. , 1994, Genes & development.

[22]  A. Breitkreutz,et al.  Dominant enhancers of Egfr in Drosophila melanogaster: genetic links between the Notch and Egfr signaling pathways. , 1997, Genetics.

[23]  Stuart K. Kim,et al.  Sequential signalling during Caenorhabditis elegans vulval induction , 1995 .

[24]  H. Horvitz,et al.  The lin-12 locus specifies cell fates in caenorhabditis elegans , 1983, Cell.

[25]  A. Jarman,et al.  Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors. , 1999, Development.