ECTOPIC EXPRESSION OF FGF-4 IN CHIMERIC MOUSE EMBRYOS INDUCES THE EXPRESSION OF EARLY MARKERS OF LIMB DEVELOPMENT IN THE LATERAL RIDGE

The biological consequences of constitutive fibroblast growth factor-4 (fgf-4) expression were investigated in chimeric embryos prepared bet ween wild-type host embryos and murine ES cells transfected with a con struct in which expression of the murine fgf-4 gene was directed by th e phosphoglycerate kinase (PGK-1) promoter. The embryos exhibit abnorm alities of the limbs and the anterior central nervous system (CNS). Th e limb phenotype comprised the induction of outgrowth along the latera l ridge between the definitive fore and hind limbs resembling the earl y phases of limb development. The CNS defects comprised a complete abs ence, or marked reduction in forebrain and midbrain structures and rud imentary or absent eye development. Constitutive expression of fgf-4 w as also accompanied by ectopic expression of the sonic hedgehog (shh) and msx-1 genes in the lateral ridge. These findings indicate that FGF exhibits multiple activities in early development which include the a bility to induce the expression of early markers of limb development i n the lateral ridge. (C) 1996 Wiley-Liss, Inc.