rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2006-4-3
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pubmed:databankReference |
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pubmed:abstractText |
Boundaries between cellular compartments often serve as signaling interfaces during embryogenesis. The coronal suture is a major growth center of the skull vault and develops at a boundary between cells derived from neural crest and mesodermal origin, forming the frontal and parietal bones, respectively. Premature fusion of these bones, termed coronal synostosis, is a common human developmental anomaly. Known causes of coronal synostosis include haploinsufficiency of TWIST1 and a gain of function mutation in MSX2. In Twist1(+/-) mice with coronal synostosis, we found that the frontal-parietal boundary is defective. Specifically, neural crest cells invade the undifferentiated mesoderm of the Twist1(+/-) mutant coronal suture. This boundary defect is accompanied by an expansion in Msx2 expression and reduction in ephrin-A4 distribution. Reduced dosage of Msx2 in the Twist1 mutant background restores the expression of ephrin-A4, rescues the suture boundary and inhibits craniosynostosis. Underlining the importance of ephrin-A4, we identified heterozygous mutations in the human orthologue, EFNA4, in three of 81 patients with non-syndromic coronal synostosis. This provides genetic evidence that Twist1, Msx2 and Efna4 function together in boundary formation and the pathogenesis of coronal synostosis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ephrin-A2,
http://linkedlifedata.com/resource/pubmed/chemical/Ephrin-A4,
http://linkedlifedata.com/resource/pubmed/chemical/Ephrins,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MSX2 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Eph Family,
http://linkedlifedata.com/resource/pubmed/chemical/Twist Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Twist1 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0964-6906
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1319-28
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16540516-Animals,
pubmed-meshheading:16540516-Base Sequence,
pubmed-meshheading:16540516-COS Cells,
pubmed-meshheading:16540516-Cells, Cultured,
pubmed-meshheading:16540516-Cercopithecus aethiops,
pubmed-meshheading:16540516-Cranial Sutures,
pubmed-meshheading:16540516-Craniosynostoses,
pubmed-meshheading:16540516-DNA-Binding Proteins,
pubmed-meshheading:16540516-Embryo, Mammalian,
pubmed-meshheading:16540516-Ephrin-A2,
pubmed-meshheading:16540516-Ephrin-A4,
pubmed-meshheading:16540516-Ephrins,
pubmed-meshheading:16540516-Gene Expression Regulation, Developmental,
pubmed-meshheading:16540516-Heterozygote,
pubmed-meshheading:16540516-Homeodomain Proteins,
pubmed-meshheading:16540516-Humans,
pubmed-meshheading:16540516-Immunohistochemistry,
pubmed-meshheading:16540516-Mesoderm,
pubmed-meshheading:16540516-Mice,
pubmed-meshheading:16540516-Mice, Inbred C57BL,
pubmed-meshheading:16540516-Mice, Transgenic,
pubmed-meshheading:16540516-Molecular Sequence Data,
pubmed-meshheading:16540516-Mutation,
pubmed-meshheading:16540516-Neural Crest,
pubmed-meshheading:16540516-Nuclear Proteins,
pubmed-meshheading:16540516-Phenotype,
pubmed-meshheading:16540516-Receptors, Eph Family,
pubmed-meshheading:16540516-Signal Transduction,
pubmed-meshheading:16540516-Tumor Cells, Cultured,
pubmed-meshheading:16540516-Twist Transcription Factor
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pubmed:year |
2006
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pubmed:articleTitle |
Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern Califoirnia Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-0176, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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