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Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis.
Hum Mol Genet 2006; 15(8):1319-28HM

Abstract

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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16540516

Citation

Merrill, Amy E., et al. "Cell Mixing at a Neural Crest-mesoderm Boundary and Deficient ephrin-Eph Signaling in the Pathogenesis of Craniosynostosis." Human Molecular Genetics, vol. 15, no. 8, 2006, pp. 1319-28.
Merrill AE, Bochukova EG, Brugger SM, et al. Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Hum Mol Genet. 2006;15(8):1319-28.
Merrill, A. E., Bochukova, E. G., Brugger, S. M., Ishii, M., Pilz, D. T., Wall, S. A., ... Maxson, R. E. (2006). Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Human Molecular Genetics, 15(8), pp. 1319-28.
Merrill AE, et al. Cell Mixing at a Neural Crest-mesoderm Boundary and Deficient ephrin-Eph Signaling in the Pathogenesis of Craniosynostosis. Hum Mol Genet. 2006 Apr 15;15(8):1319-28. PubMed PMID: 16540516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. AU - Merrill,Amy E, AU - Bochukova,Elena G, AU - Brugger,Sean M, AU - Ishii,Mamoru, AU - Pilz,Daniela T, AU - Wall,Steven A, AU - Lyons,Karen M, AU - Wilkie,Andrew O M, AU - Maxson,Robert E,Jr Y1 - 2006/03/15/ PY - 2006/3/17/pubmed PY - 2006/9/12/medline PY - 2006/3/17/entrez SP - 1319 EP - 28 JF - Human molecular genetics JO - Hum. Mol. Genet. VL - 15 IS - 8 N2 - 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. SN - 0964-6906 UR - https://www.unboundmedicine.com/medline/citation/16540516/Cell_mixing_at_a_neural_crest_mesoderm_boundary_and_deficient_ephrin_Eph_signaling_in_the_pathogenesis_of_craniosynostosis_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddl052 DB - PRIME DP - Unbound Medicine ER -