| First Author | Motch Perrine SM | Year | 2014 |
| Journal | BMC Dev Biol | Volume | 14 |
| Pages | 8 | PubMed ID | 24580805 |
| Mgi Jnum | J:208407 | Mgi Id | MGI:5563268 |
| Doi | 10.1186/1471-213X-14-8 | Citation | Motch Perrine SM, et al. (2014) Craniofacial divergence by distinct prenatal growth patterns in Fgfr2 mutant mice. BMC Dev Biol 14(1):8 |
| abstractText | BACKGROUND: Differences 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 estimates of 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 three-dimensional skull morphology, suture patency and growth. RESULTS: We show in mice what studies in humans can only infer: that specific cranial growth deviations occur prenatally and worsen with time in organisms carrying these FGFR2 mutations. We demonstrate that distinct skull morphologies of each mutation group are established by E17.5; that cranial suture patency patterns differ between mice carrying these mutations and their unaffected littermates; that the prenatal skull grows differently in each mutation group; and that unique Fgfr2-related cranial morphologies are exacerbated by late embryonic growth patterns. CONCLUSIONS: Our analysis of mutation-driven changes in cranial growth provides a previously missing piece of knowledge necessary to the explanation of variation in emergent cranial morphologies. This information is critical to the understanding of craniofacial development, disease and evolution and may contribute to the evaluation of incipient therapeutic strategies. |
