Facial development and alterations in FGF signaling in a mouse model of Crouzon Syndrome Academic Article uri icon


  • Mutations in FgfR2 cause several craniosynostosis syndromes, including Crouzon Syndrome (CS), but knowledge of the specific mechanisms by which FGF effects morphogenesis is lacking. The gene CRISPLD2 is associated with non-syndromic cleft lip/palate. Preliminary data indicate it is a novel intracellular target of FGF signaling and alters facial morphology and fibroblast migration rates in vitro. Using a FgfR2W290R mouse model of CS, we investigated the development of the CS facial phenotype and how FGFR2 activity and CRISPLD2 dosage affect cell responses to extracellular FGF. Embryos at stages E9.5-E13.5 were genotyped, photographed, sectioned, and/or used for mouse embryonic fibroblast (MEF) cell lines. Facial shape was quantified using 2-D geometric morphometrics. Cell proliferation and apoptosis in facial primordia were assayed. MEF responses to extracellular FGF were assessed using pMEK expression and cell migration vectors. MEFs were infected with a CRISPLD2 virus (or control) and tests were repeated. At E10.5 (N=104), homozygous mutants (-/-) were rarer than expected, suggesting early embryonic lethality, and had significantly narrower faces and asymmetrical maxillary processes. This is surprising given the wider faces observed in CS patients and previously demonstrated in a chick embryo model. Facial shapes in +/- and +/+ embryos did not differ significantly after accounting for allometry from E9.5-E13.5. Preliminary results show increased apoptosis in the maxillary and mandibular processes of -/- embryos. We are currently analyzing cell proliferation results and performing in vitro analyses. This work will provide insight on how upstream and downstream modulators of FGF signaling regulate craniofacial form.

published proceedings

  • The FASEB Journal

author list (cited authors)

  • Brakora, K., Ho, Y., Lainoff, A., Wong, J., Gong, S., Hallgrimsson, B., & Marcucio, R.

citation count

  • 0

complete list of authors

  • Brakora, Katherine||Ho, Yolanda||Lainoff, Alexis||Wong, Jennifer||Gong, Siew‐Ging||Hallgrimsson, Benedikt||Marcucio, Ralph

publication date

  • April 2015