Dataset Information

Embryonic craniofacial bone volume and bone mineral density in Fgfr2(+/P253R) and nonmutant mice.

ABSTRACT: Quantifying multiple phenotypic aspects of individual craniofacial bones across early osteogenesis illustrates differences in typical bone growth and maturation and provides a basis for understanding the localized and overall influence of mutations associated with disease. We quantify the typical pattern of bone growth and maturation during early craniofacial osteogenesis and determine how this pattern is modified in Fgfr2(+/P253R) Apert syndrome mice.Early differences in typical relative bone density increase are noted between intramembranous and endochondral bones, with endochondral bones normally maturing more quickly during the prenatal period. Several craniofacial bones, including the facial bones of Fgfr2(+/P253R) mice, display lower volumes during the earliest days of osteogenesis and lower relative densities until the perinatal period relative to unaffected littermates.Estimates of bone volume and linear measures describing morphology do not necessarily covary, highlighting the value of quantifying multiple facets of gross osteological phenotypes when exploring the influence of a disease causing mutation. Differences in mechanisms of osteogenesis likely underlie differences in intramembranous and endochondral relative density increase. The influence of the FGFR2 P253R mutation on bone volume changes across the prenatal period and again after birth, while its influence on relative bone density is more stable.

SUBMITTER: Percival CJ

PROVIDER: S-EPMC3998671 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Embryonic craniofacial bone volume and bone mineral density in Fgfr2(+/P253R) and nonmutant mice.

Percival Christopher J CJ Huang Yuan Y Jabs Ethylin Wang EW Li Runze R Richtsmeier Joan T JT

Developmental dynamics : an official publication of the American Association of Anatomists 20140207 4

<h4>Background</h4>Quantifying multiple phenotypic aspects of individual craniofacial bones across early osteogenesis illustrates differences in typical bone growth and maturation and provides a basis for understanding the localized and overall influence of mutations associated with disease. We quantify the typical pattern of bone growth and maturation during early craniofacial osteogenesis and determine how this pattern is modified in Fgfr2(+/P253R) Apert syndrome mice.<h4>Results</h4>Early dif ...[more]

PMID: 24504751

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Project description:BackgroundDifferences in cranial morphology arise due to changes in fundamental cell processes like migration, proliferation, differentiation and cell death driven by genetic programs. Signaling between fibroblast growth factors (FGFs) and their receptors (FGFRs) affect these processes during head development and mutations in FGFRs result in congenital diseases including FGFR-related craniosynostosis syndromes. Current research in model organisms focuses primarily on how these mutations change cell function local to sutures under the hypothesis that prematurely closing cranial sutures contribute to skull dysmorphogenesis. Though these studies have provided fundamentally important information contributing to the understanding of craniosynostosis conditions, knowledge of changes in cell function local to the sutures leave change in overall three-dimensional cranial morphology largely unexplained. Here we investigate growth of the skull in two inbred mouse models each carrying one of two gain-of-function mutations in FGFR2 on neighboring amino acids (S252W and P253R) that in humans cause Apert syndrome, one of the most severe FGFR-related craniosynostosis syndromes. We examine late embryonic skull development and suture patency in Fgfr2 Apert syndrome mice between embryonic day 17.5 and birth and quantify the effects of these mutations on 3D skull morphology, suture patency and growth.ResultsWe show in mice what studies in humans can only infer: specific cranial growth deviations occur prenatally and worsen with time in organisms carrying these FGFR2 mutations. We demonstrate that: 1) distinct skull morphologies of each mutation group are established by E17.5; 2) cranial suture patency patterns differ between mice carrying these mutations and their unaffected littermates; 3) the prenatal skull grows differently in each mutation group; and 4) unique Fgfr2-related cranial morphologies are exacerbated by late embryonic growth patterns.ConclusionsOur analysis of mutation-driven changes in cranial growth provides a previously missing piece of knowledge necessary for explaining variation in emergent cranial morphologies and may ultimately be helpful in managing human cases carrying these same mutations. This information is critical to the understanding of craniofacial development, disease and evolution and may contribute to the evaluation of incipient therapeutic strategies.

Dataset Information

Embryonic craniofacial bone volume and bone mineral density in Fgfr2(+/P253R) and nonmutant mice.

Publications

Embryonic craniofacial bone volume and bone mineral density in Fgfr2(+/P253R) and nonmutant mice.

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