Expression of Fibroblast Growth Factor Receptor-2 Splice Variants is Developmentally and Tissue-Specifically Regulated in the Amphibian Embryo

Abstract

There is increasing evidence that distinct fibroblast growth factor receptor (FGFR) genes are involved in embryonic development and that unique expression patterns of individual FGFRs correlate with tissue-specific functions. In addition, alternative splicing of mRNA transcripts from at least two of these genes (FGFR-1 and FGFR-2) can generate receptor variants with different ligand-binding specificity. By polymerase chain reaction methods and by screening a cDNA library, we have isolated five amphibian FGFR-2 splice variants which share a high degree of identity to their human counterparts. These mRNAs are developmentally regulated and are expressed in a tissue-specific manner. In particular, two alternative exons (termed IIIb and IIIc) in the second half of the third immunoglobulin-like loop are remarkably conserved and have a distinct pattern of regulation during development. Either aFGF or bFGF can activate IIIb- or IIIc-containing receptors. In contrast, KGF only activates IIIb-containing receptors. Exon IIIb-containing receptors are maternally derived mRNAs, whereas exon IIIc-containing receptors are zygotically expressed. Furthermore, their tissue distribution pattern was mutually exclusive. From the beginning of the neurula stage onward, IIIb transcripts are expressed in the epidermis, while IIIc transcripts are activated in the neuroectoderm by neural induction. At the late tail-bud stage, in situ hybridization revealed expression of IIIc mRNA in the telencephalon and the diencephalon, as well as in the head mesenchyme condensation sites originating from the proliferating neural crest cells. IIIb mRNA was detected in the epidermis and in the epithelium of the pharynx. Our data suggest that exon IIIb-containing receptors may play a role in the development of epithelial tissues, while exon IIIc-containing receptors may play a role during neural tissue formation.