{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:16:00Z","timestamp":1790727360128,"version":"4.1.0"},"reference-count":47,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["GRK 2318\/0"],"award-info":[{"award-number":["GRK 2318\/0"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["CH 1838\/1-1"],"award-info":[{"award-number":["CH 1838\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Growth arrest-specific 1 (GAS1) acts as a co-receptor to patched 1, promoting sonic hedgehog (SHH) signaling in the developing nervous system. GAS1 mutations in humans and animal models result in forebrain and craniofacial malformations, defects ascribed to a function for GAS1 in SHH signaling during early neurulation. Here, we confirm loss of SHH activity in the forebrain neuroepithelium in GAS1-deficient mice and in induced pluripotent stem cell-derived cell models of human neuroepithelial differentiation. However, our studies document that this defect can be attributed, at least in part, to a novel role for GAS1 in facilitating NOTCH signaling, which is essential to sustain a persistent SHH activity domain in the forebrain neuroepithelium. GAS1 directly binds NOTCH1, enhancing ligand-induced processing of the NOTCH1 intracellular domain, which drives NOTCH pathway activity in the developing forebrain. Our findings identify a unique role for GAS1 in integrating NOTCH and SHH signal reception in neuroepithelial cells, and they suggest that loss of GAS1-dependent NOTCH1 activation contributes to forebrain malformations in individuals carrying GAS1 mutations.<\/jats:p>","DOI":"10.1242\/dev.200080","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T14:20:18Z","timestamp":1635258018000},"source":"Crossref","is-referenced-by-count":13,"title":["GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium"],"prefix":"10.1242","volume":"148","author":[{"given":"Maike","family":"Marczenke","sequence":"first","affiliation":[{"name":"Molecular Physiology, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"},{"name":"Department of Biology, Chemistry and Pharmacy, Freie Universitaet Berlin, 12169 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Yumi","family":"Sunaga-Franze","sequence":"additional","affiliation":[{"name":"Genomics Platform, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Popp","sequence":"additional","affiliation":[{"name":"Proteomics Platform, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene W.","family":"Althaus","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Sauer","sequence":"additional","affiliation":[{"name":"Genomics Platform, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Mertins","sequence":"additional","affiliation":[{"name":"Proteomics Platform, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Christ","sequence":"additional","affiliation":[{"name":"Molecular Physiology, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-7921","authenticated-orcid":false,"given":"Thomas E.","family":"Willnow","sequence":"additional","affiliation":[{"name":"Molecular Physiology, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"},{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"2021111116214882500_DEV200080C1","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1101\/gad.1543607","article-title":"The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development","volume":"21","author":"Allen","year":"2007","journal-title":"Genes Dev."},{"key":"2021111116214882500_DEV200080C2","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.devcel.2011.04.018","article-title":"Overlapping roles and collective requirement for the coreceptors GAS1, CDO, and BOC in SHH pathway function","volume":"20","author":"Allen","year":"2011","journal-title":"Dev. 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