Fgf3 null mice are born with tail and ear defects ( Mansour, 1994) and Fgf6 mice with no apparent defect ( Fiore et al., 1997 Floss et al., 1997) targeted disruption of Fgf5 or Fgf7 leads to abnormal hair development ( Hebert et al., 1994 Guo et al., 1996), and disruption of Fgf2 alters vascular tone ( Zhou et al., 1998 Dono et al., 1998). For several FGFs however, gene knock-outs only lead to a mild abnormal phenotype.
In the mouse, experimental gene knock-outs of Fgf4 ( Rappolee et al., 1994 Feldman et al., 1995) and Fgf8 ( Meyers et al., 1998) induce a lethal phenotype. melanogaster ( Sutherland et al., 1996) and EGL-17/FGF is required for sex myoblasts migration in the nematode C. In non vertebrates, branchless/FGF is a determinant factor in the tracheal branching pattern of the fruit fly D. They are prominently involved in mesoderm induction, organ and limb formation, neural development, and branching morphogenesis (for reviews: Mason, 1994 Goldfarb, 1996). Thus, in contrast to the other nematode fgf gene egl-17, let-756/fgf is essential for worm development.įibroblast growth factors (FGFs) participate in various developmental processes and stimulate the proliferation or differentiation of a variety of cells of mesoderm, ectoderm and endoderm origin. It causes a developmental arrest early in the larval stages. A third allele, s2887, is inactivated by an inversion that disrupts the first exon. These worms are small and develop slowly into clear and scrawny, yet viable and fertile adults. The truncated protein retains the FGF core but lacks a C-terminus portion. Two partial loss-of-function alleles, s2613 and s2809, have a mutation that replaces aa 317 by a stop. Loss-of-function mutants of the let-756 gene are rescued by the wild type fgf gene in germline transformation experiments. The gene is expressed at all stages of development beyond late embryogenesis, peaking at the larval stages. We show here that this gene is transcribed and encodes a putative protein of 425 amino acids (aa). A sequence encoding a putative protein presenting 30 – 40% identity with the conserved core of vertebrate FGFs has been identified by the C. Investigating their biology in other species might be enlightening. The number of FGFs and their large range of activities have made the understanding of their precise functions difficult. In vertebrates, Fibroblast Growth Factors (FGFs) and their receptors are involved in various developmental and pathological processes, including neoplasia.
0 kommentar(er)
