Notch Inhibition of RAS Signaling Through MAP Kinase Phosphatase LIP-1 During C. elegans Vulval Development
Abstract
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.
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We thank E. Brunner, A. Dutt, E. Hafen, and R. Klemenz for critical review of the manuscript; T. Höchli and T. Bächi for their help with microscopy; A. Fire for the GFP reporter plasmids and Δpes-10 promoter; J. Wang and S. Kim for strains overexpressing mpk-1; and the Caenorhabditis elegans Genetics Center for providing some of the strains used. Supported by grants from the Sassella Foundation and the Swiss National Science Foundation (A.H.).
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Science
Volume 291 | Issue 5506
9 February 2001
9 February 2001
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Received: 11 September 2000
Accepted: 9 January 2001
Published in print: 9 February 2001
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