| Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos. | |
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MedLine Citation:
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PMID: 21557455 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Although Patch mutants show severe abnormalities in many neural crest-derived structures including the face and the heart, there is a paucity of information characterizing the mechanisms underlying these congenital defects. Via manipulating the genetic background to circumvent early embryonic lethality, our results revealed that Patch phenotypes are most likely due to a significant decrease in migratory neural crest lineage due to diminished neural crest survival and elevated apoptosis. Homozygous mutant neural crest precursors can undergo typical expansion within the neural tube, epithelial-to-mesenchymal transformation, and initiate normal neural crest emigration. Moreover, in vitro explant culture demonstrated that when isolated from the surrounding mesenchyme, Patch mutant neural crest cells (NCCs) can migrate appropriately. Additionally, Patch foregut, notochord and somitic morphogenesis, and Sonic hedgehog expression profiles were all perturbed. Significantly, the timing of lethality and extent of apoptosis correlated with the degree of severity of Patch mutant foregut, notochord, and somite dysfunction. Finally, analysis of Balb/c-enriched surviving Patch mutants revealed that not all the neural crest subpopulations are affected and that Patch mutant neural crest-derived sympathetic ganglia and dorsal root ganglia were unaffected. We hypothesize that loss of normal coordinated signaling from the notochord, foregut, and somites underlies the diminished survival of the neural crest lineage within Patch mutants resulting in subsequent neural crest-deficient phenotypes. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc. |
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Authors:
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Paige Snider; Olga Simmons; Rhonda Rogers; Rachel Young; Mica Gosnell; Simon J Conway |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-6 |
Journal Detail:
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Title: Birth defects research. Part A, Clinical and molecular teratology Volume: - ISSN: 1542-0760 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101155107 Medline TA: Birth Defects Res A Clin Mol Teratol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Developmental Biology and Neonatal Medicine Program, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana. psnider@iupui.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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