Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis.
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, respecti...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2006
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| _version_ | 1797079791001665536 |
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| author | Merrill, A Bochukova, E Brugger, S Ishii, M Pilz, D Wall, SA Lyons, K Wilkie, A Maxson, R |
| author_facet | Merrill, A Bochukova, E Brugger, S Ishii, M Pilz, D Wall, SA Lyons, K Wilkie, A Maxson, R |
| author_sort | Merrill, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:50:49Z |
| format | Journal article |
| id | oxford-uuid:8657d0c7-7a14-4624-abee-6b6270195365 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:50:49Z |
| publishDate | 2006 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:8657d0c7-7a14-4624-abee-6b62701953652022-03-26T22:03:20ZCell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8657d0c7-7a14-4624-abee-6b6270195365EnglishSymplectic Elements at OxfordOxford University Press2006Merrill, ABochukova, EBrugger, SIshii, MPilz, DWall, SALyons, KWilkie, AMaxson, RBoundaries 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. |
| spellingShingle | Merrill, A Bochukova, E Brugger, S Ishii, M Pilz, D Wall, SA Lyons, K Wilkie, A Maxson, R Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. |
| title | Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. |
| title_full | Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. |
| title_fullStr | Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. |
| title_full_unstemmed | Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. |
| title_short | Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. |
| title_sort | cell mixing at a neural crest mesoderm boundary and deficient ephrin eph signaling in the pathogenesis of craniosynostosis |
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