{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:30:34Z","timestamp":1790422234281,"version":"4.1.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,10,31]]},"abstract":"<jats:p>The telencephalic neuroepithelium (NE) of mammalian brain has an apical-basal polarity that is marked by the positioning of neural progenitors and adherens junctions on the apical\/ventricular surface and the ascending of radial glia\/progenitor fibers toward the pial\/basal surface. The signaling pathway that establishes this apical-basal polarity of NE is not completely understood, but the Rho-family GTPase Cdc42 may play a critical role because it controls cadherin-based intercellular junctions and cell polarity in many species. Here, we tested this hypothesis by a conditional gene-targeting strategy by using the Foxg1-Cre line to delete Cdc42 in the telencephalic neural progenitors in mouse embryos. We found that Cdc42-deletion abolishes the apical localization of PAR6, aPKC, E-cadherin, \u03b2-catenin, and Numb proteins in the NE, and severely impairs the extension of nestin-positive radial fibers. Consequently, neural progenitors were scattered throughout the entire depth of the NE, and the Cdc42-deficient telencephalon failed to bulge or separate into two cerebral hemispheres, resulting in holoprosencephaly. However, neither the midline expression of Sonic hedgehog nor the dorso-ventral patterning of the telencephalon was affected by Cdc42-deletion. Taken together, these results indicate that Cdc42 has an essential role in establishing the apical-basal polarity of the telencephalic NE, which is needed for the expansion and bifurcation of cerebral hemispheres.<\/jats:p>","DOI":"10.1073\/pnas.0603533103","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T20:44:50Z","timestamp":1161204290000},"page":"16520-16525","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":119,"title":["Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly"],"prefix":"10.1073","volume":"103","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"*Divisions of Experimental Hematology and"},{"name":"Molecular and Developmental Biology Graduate Program, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 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