Fibroblast growth factors (FGFs) are thought to influence many process
es in vertebrate development because of their diverse sites of express
ion and wide range of biological activities in in vitro culture system
s. As a means of elucidating embryonic functions of FGF-4, gene target
ing was used to generate mice harboring a disrupted Fgf4 gene. Embryos
homozygous for the null allele underwent uterine implantation and ind
uced uterine decidualization but did not develop substantially thereaf
ter. As was consistent with their behavior in vivo, Fgf4 null embryos
cultured in vitro displayed severely impaired proliferation of the inn
er cell mass, whereas growth and differentiation of the inner cell mas
s were rescued when null embryos were cultured in the presence of FGF-
4 protein.