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The EGF receptor in the nearest VPC sequesters the limiting EGF amounts released by the AC to prevent EGF from spreading to distal VPCs. Here, we show that not only EGFR localization in the VPCs but also EGF polarity in the AC is necessary for robust fate specification. The AC secretes EGF in a directional manner towards the nearest VPC. Loss of AC polarity causes signal spreading and, when combined with MAPK pathway hyperactivation, the ectopic induction of distal VPCs. In a screen for genes preventing distal VPC induction, we identified sra-9 and nlp-26 as genes specifically required for polarized EGF secretion. sra-9(lf) and nlp-26(lf) mutants exhibit errors in vulval fate specification, reduced precision in VPC to AC alignment and increased variability in MAPK activation. sra-9 encodes a seven-pass transmembrane receptor acting in the AC and nlp-26 a neuropeptide-like protein expressed in the VPCs. SRA-9 and NLP-26 may transduce a feedback signal to channel EGF secretion towards the nearest VPC.<\/jats:p>","DOI":"10.1242\/dev.175760","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T16:15:16Z","timestamp":1590077716000},"source":"Crossref","is-referenced-by-count":13,"title":["Polarized epidermal growth factor secretion ensures robust vulval cell fate specification in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1242","volume":"147","author":[{"given":"Louisa","family":"Mereu","sequence":"first","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"},{"name":"University and ETH Z\u00fcrich 2 Molecular Life Science PhD Program , , CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-8322","authenticated-orcid":false,"given":"Matthias K.","family":"Morf","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"},{"name":"University and ETH Z\u00fcrich 2 Molecular Life Science PhD Program , , CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvan","family":"Spiri","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"},{"name":"University and ETH Z\u00fcrich 2 Molecular Life Science PhD Program , , CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"},{"name":"University and ETH Z\u00fcrich 2 Molecular Life Science PhD Program , , CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Escobar-Restrepo","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Daube","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Walser","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-3721","authenticated-orcid":false,"given":"Alex","family":"Hajnal","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Z\u00fcrich 1 , Winterthurerstrasse 190, CH-8057 Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"2024061301315724400_DEV175760C1","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.devcel.2010.05.016","article-title":"MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans","volume":"18","author":"Alexander","year":"2010","journal-title":"Dev. 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