EXPRESSION OF RAT FIBROBLAST GROWTH-FACTOR RECEPTOR-1 AS 3 SPLICING VARIANTS DURING KIDNEY DEVELOPMENT

Fibroblast growth factors (FGF) are known to participate in the processes of embryogenesis and angiogenesis. This study was undertaken to examine the transcriptional and posttranscriptional regulation of the FGF receptor 1 (FGFR-1) subclass in the embryonic rat kidney. Two full-length FGF receptor cDNAs were cloned using low-stringency screening of a neonatal rat kidney library with a chicken FGFR-1 cDNA probe. Sequencing revealed these cloned cDNAs to be rat homologues of the FGFR-1 subtype, with the two clones representing splicing variants beta and gamma of the FGFR-1. Evidence for renal expression of a third splicing variant (alpha) was obtained by use of the polymerase chain reaction. Splicing variants alpha and beta of FGFR-1 are predicted to produce cell-surface FGF receptors with three and two immunoglobulin-like domains, respectively, whereas the gamma-isoform may represent an intracellular form of the receptor. Although all three splicing variants were expressed in the developing kidney at days 14, 17, and 20 of gestation, at neonatal days 1 and 7 and in mature rats the beta-isoform was present in vastly larger abundance than alpha- and gamma-isoforms at all stages studied. Northern blot analysis revealed enhanced expression of FGFR-1 in the neonatal compared with the mature kidney. It is concluded that FGFR-1 is expressed in the kidney predominantly as the beta-isoform splicing variant and that expression of this receptor is enhanced during kidney development.