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| Research article summary (published 27 Jan 2009): |
Early onset of craniosynostosis in an Apert mouse model reveals critical features of this pathology.
Full Abstract
Activating mutations of FGFRs1-3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form.
Author information
Author/s: Holmes, Greg (G); Rothschild, Gerson (G); Roy, Upal Basu (UB); Deng, Chu-Xia (CX); Mansukhani, Alka (A); Basilico, Claudio (C);
Affiliation: Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Grants: AR051358 (Agency:NIAMS NIH HHS)
Journal and publication information
Publication Type: Journal Article; Research Support, N.I.H., Extramural
Journal: Developmental biology (Dev Biol), published in United States. (Language: eng)
Reference: 2009-Apr; vol 328 (issue 2) : pp 273-84
Dates: Created 2009/04/27; Completed 2009/06/09;
PMID: 19389359, status: MEDLINE (last retrieval date: 6/9/2009, IMS Date: 09 Jun 2009 00:00:00)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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