Tags

Type your tag names separated by a space and hit enter

Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome.
Dev Biol 2012; 368(2):283-93DB

Abstract

Coordinated growth of the skull and brain are vital to normal human development. Craniosynostosis, the premature fusion of the calvarial bones of the skull, is a relatively common pediatric disease, occurring in 1 in 2500 births, and requires significant surgical management, especially in syndromic cases. Syndromic craniosynostosis is caused by a variety of genetic lesions, most commonly by activating mutations of FGFRs 1-3, and inactivating mutations of TWIST1. In a mouse model of TWIST1 haploinsufficiency, cell mixing between the neural crest-derived frontal bone and mesoderm-derived parietal bone accompanies coronal suture fusion during embryonic development. However, the relevance of lineage mixing in craniosynostosis induced by activating FGFR mutations is unknown. Here, we demonstrate a novel mechanism of suture fusion in the Apert Fgfr2(S252W) mouse model. Using Cre/lox recombination we simultaneously induce expression of Fgfr2(S252W) and β-galactosidase in either the neural crest or mesoderm of the skull. We show that mutation of the mesoderm alone is necessary and sufficient to cause craniosynostosis, while mutation of the neural crest is neither. The lineage border is not disrupted by aberrant cell migration during fusion. Instead, the suture mesenchyme itself remains intact and is induced to undergo osteogenesis. We eliminate postulated roles for dura mater or skull base changes in craniosynostosis. The viability of conditionally mutant mice also allows post-natal assessment of other aspects of Apert syndrome.

Authors+Show Affiliations

Department of Microbiology, New York University School of Medicine, 550 1st Ave, New York, NY 10016, USA. gregory.holmes@exchange.mssm.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22664175

Citation

Holmes, Greg, and Claudio Basilico. "Mesodermal Expression of Fgfr2S252W Is Necessary and Sufficient to Induce Craniosynostosis in a Mouse Model of Apert Syndrome." Developmental Biology, vol. 368, no. 2, 2012, pp. 283-93.
Holmes G, Basilico C. Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome. Dev Biol. 2012;368(2):283-93.
Holmes, G., & Basilico, C. (2012). Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome. Developmental Biology, 368(2), pp. 283-93. doi:10.1016/j.ydbio.2012.05.026.
Holmes G, Basilico C. Mesodermal Expression of Fgfr2S252W Is Necessary and Sufficient to Induce Craniosynostosis in a Mouse Model of Apert Syndrome. Dev Biol. 2012 Aug 15;368(2):283-93. PubMed PMID: 22664175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome. AU - Holmes,Greg, AU - Basilico,Claudio, Y1 - 2012/06/01/ PY - 2012/02/07/received PY - 2012/04/19/revised PY - 2012/05/22/accepted PY - 2012/6/6/entrez PY - 2012/6/6/pubmed PY - 2012/10/30/medline SP - 283 EP - 93 JF - Developmental biology JO - Dev. Biol. VL - 368 IS - 2 N2 - Coordinated growth of the skull and brain are vital to normal human development. Craniosynostosis, the premature fusion of the calvarial bones of the skull, is a relatively common pediatric disease, occurring in 1 in 2500 births, and requires significant surgical management, especially in syndromic cases. Syndromic craniosynostosis is caused by a variety of genetic lesions, most commonly by activating mutations of FGFRs 1-3, and inactivating mutations of TWIST1. In a mouse model of TWIST1 haploinsufficiency, cell mixing between the neural crest-derived frontal bone and mesoderm-derived parietal bone accompanies coronal suture fusion during embryonic development. However, the relevance of lineage mixing in craniosynostosis induced by activating FGFR mutations is unknown. Here, we demonstrate a novel mechanism of suture fusion in the Apert Fgfr2(S252W) mouse model. Using Cre/lox recombination we simultaneously induce expression of Fgfr2(S252W) and β-galactosidase in either the neural crest or mesoderm of the skull. We show that mutation of the mesoderm alone is necessary and sufficient to cause craniosynostosis, while mutation of the neural crest is neither. The lineage border is not disrupted by aberrant cell migration during fusion. Instead, the suture mesenchyme itself remains intact and is induced to undergo osteogenesis. We eliminate postulated roles for dura mater or skull base changes in craniosynostosis. The viability of conditionally mutant mice also allows post-natal assessment of other aspects of Apert syndrome. SN - 1095-564X UR - https://www.unboundmedicine.com/medline/citation/22664175/Mesodermal_expression_of_Fgfr2S252W_is_necessary_and_sufficient_to_induce_craniosynostosis_in_a_mouse_model_of_Apert_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-1606(12)00285-0 DB - PRIME DP - Unbound Medicine ER -