Document Detail

Protein tyrosine phosphatase activity in the neural crest is essential for normal heart and skull development.
MedLine Citation:
PMID:  19541608     Owner:  NLM     Status:  MEDLINE    
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.
Tomoki Nakamura; James Gulick; Melissa C Colbert; Jeffrey Robbins
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-06-18
Journal Detail:
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:
Created Date:  2009-07-08     Completed Date:  2009-07-27     Revised Date:  2010-09-24    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11270-5     Citation Subset:  IM    
Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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MeSH Terms
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, Knockout
Neural Crest / cytology,  embryology*,  enzymology*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
Skull / embryology*,  enzymology*
Grant Support
Reg. No./Substance:
EC Signal-Regulated MAP Kinases; EC Tyrosine Phosphatase, Non-Receptor Type 11

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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