FGF2 promotes skeletogenic differentiation of cranial neural crest cells

The cranial neural crest gives rise to most of the skeletal tissues of the skull. Matrix-mediated tissue interactions have been implicated in the skel etogenic differentiation of crest cells, but little is known of the role th at growth factors might play in this process. The discovery that mutations in fibroblast growth factor receptors (FGFRs) cause the major craniosynosto sis syndromes implicates FGF-mediated signalling in the skeletogenic differ entiation of the cranial neural crest. We now show that, in vitro, mesencep halic neural crest cells respond to exogenous FGF2 in a dose-dependent mann er, with 0.1 and 1 ng/ml causing enhanced proliferation, and 10 ng/ml induc ing cartilage differentiation. In longer-term cultures, both endochondral a nd membrane bone are formed. FGFR1, FGFR2 and FGFR3 are all detectable by i mmunohistochemistry in the mesencephalic region, with particularly intense expression at the apices of the neural folds from which the neural crest ar ises. FGFRs are also expressed by subpopulations of neural crest cells in c ulture. Collectively, these findings suggest that FGFs are involved in the skeletogenic differentiation of the cranial neural crest.