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Published on: February 7, 2012
FGF2 promotes skeletogenic differentiation of cranial neural crest cells
1Developmental Biology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK.
Abstract:
The cranial neural crest gives rise to most of the skeletal tissues of the skull. Matrix-mediated tissue interactions have been implicated in the skeletogenic differentiation of crest cells, but little is known of the role that growth factors might play in this process. The discovery that mutations in fibroblast growth factor receptors (FGFRs) cause the major craniosynostosis syndromes implicates FGF-mediated signalling in the skeletogenic differentiation of the cranial neural crest. We now show that, in vitro, mesencephalic neural crest cells respond to exogenous FGF2 in a dose-dependent manner, with 0.1 and 1 ng/ml causing enhanced proliferation, and 10 ng/ml inducing cartilage differentiation. In longer-term cultures, both endochondral and membrane bone are formed. FGFR1, FGFR2 and FGFR3 are all detectable by immunohistochemistry in the mesencephalic region, with particularly intense expression at the apices of the neural folds from which the neural crest arises. FGFRs are also expressed by subpopulations of neural crest cells in culture. Collectively, these findings suggest that FGFs are involved in the skeletogenic differentiation of the cranial neural crest.
Insights
Fibroblast growth factors (FGFs) are crucial for cranial neural crest cell differentiation into skull bones. FGF2 signaling promotes proliferation and cartilage formation, indicating FGFs
Area of Science:
- Developmental Biology
- Craniofacial Development
- Cell Signaling
Background:
- The cranial neural crest is essential for forming most skull skeletal tissues.
- Matrix interactions are known to influence skeletogenic differentiation, but the role of growth factors is less understood.
- Mutations in fibroblast growth factor receptors (FGFRs) are linked to craniosynostosis syndromes, suggesting FGF signaling involvement.
Purpose of the Study:
- To investigate the role of fibroblast growth factors (FGFs) in the skeletogenic differentiation of cranial neural crest cells.
- To determine the effects of FGF2 on neural crest cell proliferation and differentiation in vitro.
- To examine the expression of FGFRs in the developing cranial neural crest.
Main Methods:
- In vitro culture of mesencephalic neural crest cells.
- Treatment with varying concentrations of exogenous FGF2.
- Immunohistochemical analysis of FGFR expression in the mesencephalic region and cultured neural crest cells.
Main Results:
- Exogenous FGF2 enhanced proliferation of neural crest cells at low doses (0.1 and 1 ng/ml).
- Higher FGF2 concentration (10 ng/ml) induced cartilage differentiation.
- Both endochondral and membrane bone formation were observed in longer-term cultures.
- FGFR1, FGFR2, and FGFR3 were detected in the mesencephalic region and on neural crest cells in culture.
Conclusions:
- FGF signaling plays a significant role in the skeletogenic differentiation of cranial neural crest cells.
- FGF2 directly influences neural crest cell proliferation and differentiation towards bone formation.
- FGFR expression patterns suggest an autocrine or paracrine role for FGF signaling in cranial skeletogenesis.
