| Protein tyrosine phosphatase activity in the neural crest is essential for normal heart and skull development. | |
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MedLine Citation:
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PMID: 19541608 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutations within the protein tyrosine phosphatase, SHP2, which is encoded by PTPN11, cause a significant proportion of Noonan syndrome (NS) cases, typically presenting with both cardiac disease and craniofacial abnormalities. Neural crest cells (NCCs) participate in both heart and skull formation, but the role of SHP2 signaling in NCC has not yet been determined. To gain insight into the role of SHP2 in NCC function, we ablated PTPN11 specifically in premigratory NCCs. SHP2-deficient NCCs initially exhibited normal migratory and proliferative patterns, but in the developing heart failed to migrate into the developing outflow tract. The embryos displayed persistent truncus arteriosus and abnormalities of the great vessels. The craniofacial deficits were even more pronounced, with large portions of the face and cranium affected, including the mandible and frontal and nasal bones. The data show that SHP2 activity in the NCC is essential for normal migration and differentiation into the diverse lineages found in the heart and skull and demonstrate the importance of NCC-based normal SHP2 activity in both heart and skull development, providing insight into the syndromic presentation characteristic of NS. |
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Authors:
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Tomoki Nakamura; James Gulick; Melissa C Colbert; Jeffrey Robbins |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-06-18 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-08 Completed Date: 2009-07-27 Revised Date: 2010-09-24 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 11270-5 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Cell Movement Craniofacial Abnormalities / enzymology, pathology Down-Regulation / genetics Embryo, Mammalian / enzymology, pathology Enzyme Activation Extracellular Signal-Regulated MAP Kinases / metabolism Gene Deletion Heart / embryology* Heart Defects, Congenital / enzymology, pathology Mice Mice, Knockout Neural Crest / cytology, embryology*, enzymology* Phenotype Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism* Skull / embryology*, enzymology* |
| Grant Support | |
ID/Acronym/Agency:
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P01HL059408/HL/NHLBI NIH HHS; P01HL69799/HL/NHLBI NIH HHS; P50HL07701/HL/NHLBI NIH HHS; R01HL087862/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11 |
| Comments/Corrections | |
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