cDNA Cloning and Developmental Expression of Fibroblast Growth Factor Receptors from Xenopus laevis

Abstract

The heparin-binding growth factors constitute a family of homologous polypeptides including basic and acidic fibroblast growth factors (FGFs). These factors participate in a variety of processes, including wound healing, angiogenesis, neuronal survival, and inductive events in the early amphibian embryo. We have isolated three closely related species of cDNA clones for Xenopus FGF receptors. One of these, designated XFGFR-A1, encodes an open reading frame of 814 amino acids. A second class encodes an identical amino acid sequence with the exception of an 88-amino-acid deletion near the 5' end. This species probably arises through alternative splicing. A third class of cDNA corresponding to the shorter form of XFGFR-A1 was isolated and shown to be 95% homologous and is designated XFGFR-A2. Xenopus FGF receptors are similar to FGF receptors from other species in that they contain a transmembrane domain, a tyrosine kinase domain split by a 14-amino-acid insertion, and a unique conserved stretch of eight acidic residues in the extracellular domain. Overexpression of Xenopus FGF receptor protein by transfection of COS1 cells with the corresponding cDNA in a transient expression vector leads to the appearance of new FGF binding sites on transfected cells, consistent with these cDNAs encoding for FGF receptors. RNA gel blot analysis demonstrates that Xenopus FGF receptor mRNA is a maternal message and is expressed throughout early development. When blastula-stage ectoderm is cultured in control amphibian salt solutions, Xenopus FGF receptor mRNA declines to undetectable levels by late neurula stages. However, when cultured in the presence of FGF of XTC mesoderm-inducing factor, Xenopus FGF receptor RNA expression is maintained.

Essential role of heparan sulfates in axon navigation and targeting in the developing visual system

“…Thus, the bypass phenotype seen with the exogenous application of this specific HS may result from it uniquely interfering with the endogenous interaction of FGF-2 with only one of the four families of FGFRs. FGFR-1 is present in the developing Xenopus eye primordium (Friesel and Dawid, 1991; M. Zuber and C. E. Holt, unpublished data), raising the possibility that the interaction between FGF-2 and FGFR-1 is specifically required for retinal axon target recognition. One of the striking features of the bypass phenotype induced by HS(FGF-2) is its robust penetrance.…”