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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.

pediatric research

Pleiotropic Features of Syndromic Craniosynostoses Correlate with Differential Expression of Fibroblast Growth Factor Receptors 1 and 2 during Human Craniofacial Development