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• W2759102812 endingPage "1488" @default.
• W2759102812 startingPage "1473" @default.
• W2759102812 abstract "Abstract Six initially equivalent, multipotential Vulval Precursor Cells (VPCs) in Caenorhabditis elegans adopt distinct cell fates in a precise spatial pattern, with each fate associated with transcription of different target genes. The pattern is centered on a cell that adopts the “1°” fate through Epidermal Growth Factor Receptor (EGFR) activity, and produces a lateral signal composed of ligands that activate LIN-12/Notch in the two flanking VPCs to cause them to adopt “2°” fate. Here, we investigate orthologs of a transcription complex that acts in mammalian EGFR signaling—lin-1/Elk1, sur-2/Med23, and the Cdk8 Kinase module (CKM)—previously implicated in aspects of 1° fate in C. elegans and show they act in different combinations for different processes for 2° fate. When EGFR is inactive, the CKM, but not SUR-2, helps to set a threshold for LIN-12/Notch activity in all VPCs. When EGFR is active, all three factors act to resist LIN-12/Notch, as revealed by the reduced ability of ectopically-activated LIN-12/Notch to activate target gene reporters. We show that overcoming this resistance in the 1° VPC leads to repression of lateral signal gene reporters, suggesting that resistance to LIN-12/Notch helps ensure that P6.p becomes a robust source of the lateral signal. In addition, we show that sur-2/Med23 and lin-1/Elk1, and not the CKM, are required to promote endocytic downregulation of LIN-12-GFP in the 1° VPC. Finally, our analysis using cell fate reporters reveals that both EGFR and LIN-12/Notch signal transduction pathways are active in all VPCs in lin-1/Elk1 mutants, and that lin-1/Elk1 is important for integrating EGFR and lin-12/Notch signaling inputs in the VPCs so that the proper gene complement is transcribed." @default.
• W2759102812 created "2017-10-06" @default.
• W2759102812 creator A5008533853 @default.
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• W2759102812 date "2017-09-27" @default.
• W2759102812 modified "2023-10-01" @default.
• W2759102812 title "Integration of EGFR and LIN-12/Notch Signaling by LIN-1/Elk1, the Cdk8 Kinase Module, and SUR-2/Med23 in Vulval Precursor Cell Fate Patterning in <i>Caenorhabditis elegans</i>" @default.
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• W2759102812 doi "https://doi.org/10.1534/genetics.117.300192" @default.
• W2759102812 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5714460" @default.
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• W2759102812 hasPublicationYear "2017" @default.
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