Immunolocalization of fibroblast growth factor receptors 1 and 2 in mouse palate development

Recent evidence has implicated mutations of fibroblast growth factor recept ors (FGF-R) in the pathogenesis of craniosynostotic syndromes. Cleft palate can be a component of such syndromes. The expression of FGF-R1 and FGF-R2 has been delineated in normally developing cranium, where they seem to regu late cellular differentiation and proliferation, respectively. The specific role of fibroblast growth factor signaling in mammalian palate development is unclear. The authors investigated the patterns of expression of FGF-RI and FGF-R2 throughout mouse palatal development in the embryo. Time-dated C D-1 mouse heads (n = 135) were harvested at embryonic ages 12.5, 13.5, 14.5 , 15.5, and 16.5 days (term gestation = 19.5 days), fixed in paraformaldehy de, embedded in paraffin, and sectioned. In addition, paired palatal shelve s (n = 30) were isolated by means of microdissection from embryonic day-13. 5 embryos, grown on Millipore filters in serum-free medium in vitro for 24, 48, 72, or 96 hours and processed for histological analysis. Immunohistoch emical analysis for FGF-R1 and FGF-R2 was performed on the in vivo and in v itro specimens. FGF-R1 and FGF-R2 were found to be specifically expressed i n the epithelium of the developing palatal shelves from the time of their o utgrowth from the maxillary processes through completion of fusion in vivo and in vitro. Expression of both receptors was particularly strong during t he phases of medial epithelial-medial epithelial contact between the indivi dual shelves, through the formation of the medial epithelial seam, to the u ltimate dissolution of the seam. Such a pattern of expression seems to impl icate fibroblast growth factor signaling in the regulation of the critical phase of fusion of the bilateral shelves. The expression of both FGF-R1 and FGF-R2 in the lateral palatal mesenchyme, where such secondary structures as tooth primordia and bone begin to appear, also suggests a role for fibro blast growth factor signaling in the induction of ongoing differentiation a nd maturation of the palate after fusion. These data suggest that fibroblas t growth factor signaling may play a role in the epithelial-mesenchymal int eractions that dictate fusion and maturation of the developing palate. Furt hermore, the data are consistent with the correlation of cleft palate forma tion with aberrant fibroblast growth factor signaling.