{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T15:47:30Z","timestamp":1762098450287},"reference-count":57,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":2978,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Holoprosencephaly is the most common forebrain defect in humans. We describe two novel mouse mutants that display a holoprosencephaly-like phenotype. Both mutations disrupt genes in the glycerophosphatidyl inositol (GPI) biosynthesis pathway: gonzo disrupts Pign and beaker disrupts Pgap1. GPI anchors normally target and anchor a diverse group of proteins to lipid raft domains. Mechanistically we show that GPI anchored proteins are mislocalized in GPI biosynthesis mutants. Disruption of the GPI-anchored protein Cripto (mouse) and TDGF1 (human ortholog) have been shown to result in holoprosencephaly, leading to our hypothesis that Cripto is the key GPI anchored protein whose altered function results in an HPE-like phenotype. Cripto is an obligate Nodal co-factor involved in TGF\u03b2 signaling, and we show that TGF\u03b2 signaling is reduced both in vitro and in vivo. This work demonstrates the importance of the GPI anchor in normal forebrain development and suggests that GPI biosynthesis genes should be screened for association with human holoprosencephaly.<\/jats:p>","DOI":"10.1242\/bio.20121982","type":"journal-article","created":{"date-parts":[[2012,7,21]],"date-time":"2012-07-21T13:27:32Z","timestamp":1342877252000},"page":"874-883","source":"Crossref","is-referenced-by-count":46,"title":["Defects in GPI biosynthesis perturb Cripto signaling during forebrain development in two new mouse models of holoprosencephaly"],"prefix":"10.1242","volume":"1","author":[{"given":"David M.","family":"McKean","sequence":"first","affiliation":[{"name":"HHMI, Department of Pediatrics, Cell Biology, Stem Cells and Development Graduate Program, and Children's Hospital Colorado, University of Colorado Anschutz Medical Campus Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Niswander","sequence":"additional","affiliation":[{"name":"HHMI, Department of Pediatrics, Cell Biology, Stem Cells and Development Graduate Program, and Children's Hospital Colorado, University of Colorado Anschutz Medical Campus Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2012,7,9]]},"reference":[{"key":"2021080923312034600_b1","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":"2021080923312034600_b2","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ydbio.2006.02.002","article-title":"Synergistic interaction between Gdf1 and Nodal during anterior axis development.","volume":"293","author":"Andersson","year":"2006","journal-title":"Dev. 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