| The ciliogenic protein Oral-Facial-Digital 1 regulates the neuronal differentiation of embryonic stem cells. | |
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MedLine Citation:
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PMID: 20873986 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oral-Facial-Digital 1 (OFD1) Syndrome is an X-linked developmental disorder caused by mutations in the gene Ofd1. OFD1 syndrome involves malformation of the face, oral cavity, and digits and may be characterized by cystic kidneys and mental retardation. Deletion or missense mutations in Ofd1 also result in loss of primary cilia, a microtubule-based cellular projection that mediates multiple signaling pathways. Ofd1 mutant mice display pleiotropic developmental phenotypes, including neural, skeletal, and cardiac defects. To address how loss of Ofd1 and loss of primary cilia affect early differentiation decisions, we analyzed embryoid bodies (EBs) derived from Ofd1 mutant embryonic stem (ES) cells. Ofd1 mutant EBs do not form primary cilia and display defects in Hedgehog and Wnt signaling. Additionally, we show that ES cells lacking Ofd1 display an increased capacity to differentiate into neurons. Nevertheless, neurons derived from Ofd1 mutant ES cells fail to differentiate into V3 interneurons, a cell type dependent on ciliary function and Hedgehog signaling. Thus, loss of Ofd1 affects ES cell interpretation of developmental cues and reveals that EBs model some aspects of ciliopathies, providing insights into the developmental origins of OFD1 syndrome and functions of cilia. |
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Authors:
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Julie Hunkapiller; Veena Singla; Allen Seol; Jeremy F Reiter |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-30 |
Journal Detail:
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Title: Stem cells and development Volume: 20 ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-06 Completed Date: 2011-09-13 Revised Date: 2012-05-01 |
Medline Journal Info:
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Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: United States |
Other Details:
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Languages: eng Pagination: 831-41 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / genetics* Cilia / genetics, metabolism, pathology* Disease Models, Animal Embryoid Bodies / metabolism*, pathology Female Gene Expression Regulation, Developmental Genetic Diseases, X-Linked / metabolism, pathology Hedgehog Proteins / genetics, metabolism Mice Mice, Transgenic Mutation Neurons / metabolism*, pathology Orofaciodigital Syndromes / genetics, metabolism*, pathology* Proteins / genetics, metabolism* Signal Transduction Wnt Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01AR054396/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hedgehog Proteins; 0/OFD1 protein, mouse; 0/Proteins; 0/Wnt Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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