{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T07:44:15Z","timestamp":1784619855057,"version":"3.55.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T00:00:00Z","timestamp":1506470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 \u201c1\u00b0\u201d 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 \u201c2\u00b0\u201d fate. Here, we investigate orthologs of a transcription complex that acts in mammalian EGFR signaling\u2014lin-1\/Elk1, sur-2\/Med23, and the Cdk8 Kinase module (CKM)\u2014previously implicated in aspects of 1\u00b0 fate in C. elegans and show they act in different combinations for different processes for 2\u00b0 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\u00b0 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\u00b0 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.<\/jats:p>","DOI":"10.1534\/genetics.117.300192","type":"journal-article","created":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T00:10:44Z","timestamp":1506557444000},"page":"1473-1488","source":"Crossref","is-referenced-by-count":23,"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>"],"prefix":"10.1093","volume":"207","author":[{"given":"Ryan S","family":"Underwood","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics , Columbia University Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences , Columbia University, New York, New York 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics , Columbia University Medical Center, New York, New York 10032"},{"name":"Department of Biological Sciences , Columbia University, New York, New York 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,27]]},"reference":[{"key":"2022110414555600700_bib1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1534\/genetics.113.160846","article-title":"Simultaneous expression of multiple proteins under a single promoter in Caenorhabditis elegans via a versatile 2A-based toolkit.","volume":"196","author":"Ahier","year":"2014","journal-title":"Genetics"},{"key":"2022110414555600700_bib2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/35024111","article-title":"TFIIH is negatively regulated by cdk8-containing mediator complexes.","volume":"407","author":"Akoulitchev","year":"2000","journal-title":"Nature"},{"key":"2022110414555600700_bib3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrm3951","article-title":"The mediator complex: a central integrator of transcription.","volume":"16","author":"Allen","year":"2015","journal-title":"Nat. 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