Abstract
Mutations in FGFR1, -2, and -3 are linked to five human craniosynostosis syndromes. In addition to premature fusion of cranial sutures, nonskeletal manifestations in skin, and teeth together with CNS abnormalities, reflect widespread effects of these mutations. To understand this pleiotropy, we have assessed craniofacial FGFR1 and -2 expression in the human embryo from 6 wk postfertilization. We found that both genes are expressed in sheets of condensed mesenchyme before overt chondrogenic differentiation and that distinct patterns of expression are established by 8 wk. Thus, FGFR2(BEK) is expressed evenly throughout developing cartilage and bone, whereas FGFR1 transcripts predominate in perichondria and periostea. Complementary patterns of FGFR1 and FGFR2(BEK and KGFR) expression are also observed in the enamel epithelium and papilla mesenchyme of the tooth germ, at a stage when morphogenetic tissue interactions ensue. Both genes are expressed in the cortical layer of the brain, but expression levels vary significantly within the choroid plexus and wall of the fourth ventricle. Similarly, tissue-specific differences in receptor expression are found in both the skin and salivary glands. These expression data are consistent with the pleiotropic manifestations of syndromic craniosynostoses and provide the basis for a new paradigm to explain the associated CNS problems.
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Abbreviations
- FGFR:
-
fibroblast growth factor receptor
- FGF:
-
fibroblast growth factor
- KGFR:
-
keratinocyte growth factor receptor
- ICP:
-
intracranial pressure
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Acknowledgements
The authors thank colleagues Robin Winter, Richard Hayward, Rachel Moore, Jonathan Britto, and Sanjukta Sarker for their comments on the manuscript and to all staff involved in the running of the Human Embryonic Tissue Bank, which is funded by the Medical Research Council (United Kingdom).
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This work was funded by a grant from the Birth Defects Foundation (to P.T.).
This paper is dedicated to Prof. Peter Thorogood who died recently in a climbing accident. He set the standard for all his junior staff in his rigorous approach to science and in his personal behavior. He always seemed to find the time to listen to an issue no matter how trivial it seemed, despite his pressing schedule. He will be sorely missed by all of us.
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Chan, CT., Thorogood, P. Pleiotropic Features of Syndromic Craniosynostoses Correlate with Differential Expression of Fibroblast Growth Factor Receptors 1 and 2 during Human Craniofacial Development. Pediatr Res 45, 46–53 (1999). https://doi.org/10.1203/00006450-199901000-00008
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DOI: https://doi.org/10.1203/00006450-199901000-00008
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