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Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure

Ahlgren, Sara C. and Thakur, Vijaya and Bronner-Fraser, Marianne (2002) Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. Proceedings of the National Academy of Sciences of the United States of America, 99 (16). pp. 10476-10481. ISSN 0027-8424. PMCID PMC124946.

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Alcohol is a teratogen that induces a variety of abnormalities including brain and facial defects [Jones, K. & Smith, D. (1973) Lancet 2, 999-1001], with the exact nature of the deficit depending on the time and magnitude of the dose of ethanol to which developing fetuses are exposed. In addition to abnormal facial structures, ethanol-treated embryos exhibit a highly characteristic pattern of cell death. Dying cells are observed in the premigratory and migratory neural crest cells that normally populate most facial structures. The observation that blocking Sonic hedgehog (Shh) signaling results in similar craniofacial abnormalities prompted us to examine whether there was a link between this aspect of fetal alcohol syndrome and loss of Shh. We demonstrate that administration of ethanol to chick embryos results in a dramatic loss of Shh, as well as a loss of transcripts involved in Shh signaling pathways. In contrast, other signaling molecules examined do not demonstrate such dramatic changes. Furthermore, we demonstrate that both the ethanol-induced cranial neural crest cell death and the associated craniofacial growth defect can be rescued by application of Shh. These data suggest that craniofacial anomalies resulting from fetal alcohol exposure are caused at least partially by loss of Shh and subsequent neural crest cell death.

Item Type:Article
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URLURL TypeDescription CentralArticle
Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:Copyright © 2002 by the National Academy of Sciences Communicated by Eric H. Davidson, California Institute of Technology, Pasadena, CA and approved June 14, 2002 (received for review March 14, 2002) We thank Sarah Mahoney for technical assistance, Laura Gammill and Tanya Moreno for advice, and Clare Baker and Martin Garcia-Castro for reading the manuscript. We extend many thanks to Drs. Cliff Tabin, Juan Carlos Izpisua-Belmonte, and Mary Dickinson for materials. S.C.A. was supported by an American Heart Association fellowship, Award 1168-F11, as well as by National Institutes of Health Grant USPHS NS36585, awarded to M.B.-F.
Funding AgencyGrant Number
American Heart Association1168-F11
Issue or Number:16
PubMed Central ID:PMC124946
Record Number:CaltechAUTHORS:AHLpnas02
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4928
Deposited By: Archive Administrator
Deposited On:13 Sep 2006
Last Modified:02 Oct 2019 23:17

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