| First Author | Lee KKL | Year | 2018 |
| Journal | Dis Model Mech | Volume | 11 |
| Issue | 11 | PubMed ID | 30266836 |
| Mgi Jnum | J:267761 | Mgi Id | MGI:6258140 |
| Doi | 10.1242/dmm.035311 | Citation | Lee KKL, et al. (2018) Overexpression of Fgfr2c causes craniofacial bone hypoplasia and ameliorates craniosynostosis in the Crouzon mouse. Dis Model Mech 11(11):dmm035311 |
| abstractText | FGFR2c regulates many aspects of craniofacial and skeletal development. Mutations in the FGFR2 gene are causative of multiple forms of syndromic craniosynostosis, including Crouzon syndrome. Paradoxically, mouse studies have shown that the activation (Fgfr2c (C342Y); a mouse model for human Crouzon syndrome), as well as the removal (Fgfr2c (null)), of the FGFR2c isoform can drive suture abolishment. This study aims to address the downstream effects of pathogenic FGFR2c signalling by studying the effects of Fgfr2c overexpression. Conditional overexpression of Fgfr2c (R26R (Fgfr2c;betaact)) results in craniofacial hypoplasia as well as microtia and cleft palate. Contrary to Fgfr2c (null) and Fgfr2c (C342Y), Fgfr2c overexpression is insufficient to drive onset of craniosynostosis. Examination of the MAPK/ERK pathway in the embryonic sutures of Fgfr2c (C342Y) and R26R (Fgfr2c;betaact) mice reveals that both mutants have increased pERK expression. The contrasting phenotypes between Fgfr2c (C342Y) and R26R (Fgfr2c;betaact) mice prompted us to assess the impact of the Fgfr2c overexpression allele on the Crouzon mouse (Fgfr2c (C342Y)), in particular its effects on the coronal suture. Our results demonstrate that Fgfr2c overexpression is sufficient to partially rescue craniosynostosis through increased proliferation and reduced osteogenic activity in E18.5 Fgfr2c (C342Y) embryos. This study demonstrates the intricate balance of FGF signalling required for correct calvarial bone and suture morphogenesis, and that increasing the expression of the wild-type FGFR2c isoform could be a way to prevent or delay craniosynostosis progression. |
