In several different species, fibroblast growth factors (FGFs) have been shown to be involved in many different aspects of cell behavior, including promotion of mitogenesis, cell migration, and induction of specific cell fates. We have been interested in the roles that FGF signaling might have in the induction and patterning of the developing mesoderm lineage in the vertebrate embryo. Studies in Xenopus laevis first implicated FGFs in mesoderm development. Exogenous basic FGF, when added to animal cap explants, is able to induce mesoderm from tissue normally fated to become ectoderm (Kimelman and Kirschner 1987; Paterno et al. 1989; Slack et al. 1989). The introduction of a dominant-negative FGF receptor into Xenopus embryos at various stages of development has demonstrated that FGF signaling is required for the expression of several early mesodermal markers, for the induction of posterior and ventral mesoderm, and for proper mesodermal maintenance during gastrulation (Amaya et al. 1991, 1993; Kroll and Amaya 1996). These kinds of studies indicate a general role for FGF signaling in mesoderm development, but they do not specify the relative roles of the different receptors and ligands that might be expressed in the intact embryo. In vertebrates, there are more than ten different FGFs and four different receptors, each with differently spliced isoforms. In the mouse, it has been shown that FGFs 3, 4, 5, and 8 are expressed within the primitive streak in spatial and temporal patterns, which would be consistent with a role for FGF signaling in mesoderm induction or in regulating processes of fate determination (Wilkinson et al. 1988; Haub and Goldfarb 1991; Hebert et al. 1991; Niswander and Martin 1992; Crossley and Martin 1995). So far, the published mutations in relevant FGFs have not shed much light on their possible roles in gastrulation. Mutations in Fgf3 and Fgf5 led to late defects in ear and tail development and in the hair growth cycle, respectively (Mansour et al. 1993; Hebert et al. 1994). Targeted disruption of Fgf4 resulted in peri-implantation lethality prior to mesoderm formation (Feldman et al. 1995). None of these studies definitively exclude any of the FGFs from acting at gastrulation, since there is clear overlap in expression and known cross-specificity in ligand-receptor interactions (Ornitz et al. 1996). Given the large number of ligands and the extensive cross-talk in the FGF system, we have focused on trying to assess the role of FGF signaling in mesoderm development by studying the roles of the receptors, which are fewer in number and also restricted in their expression. Fgfrl is first expressed throughout the primitive ectoderm. In mid-streak-staged embryos, Fgfrl expression is concentrated in the posterior mesoderm lateral to the primitive streak and is maintained in the migrating mesodermal wings; headfold stage embryos show strong expression in both neurectoderm and the developing paraxial mesoderm (Orr-Urtreger et al. 1991; Yamaguchi et al. 1992). Targeted mutation of Fgfrl resulted in embryonic lethality between day 7.5 and day 9.5 of development, with defects first manifesting themselves at the onset of gastrulation (Deng et al. 1994; Yamaguchi et al. 1994). Homozygous Fgfrl mutant embryos showed complex morphological abnormalities, including thickening of the posterior streak suggestive of defects in cell behavior within the primitive streak. Paraxial mesoderm of Fgfrl mutant embryos was much reduced, yet axial mesoderm was still present and possibly expanded, suggesting that FGFR 1 might also have a role in patterning the mesoderm populations arising at different positions along the streak (Deng et al. 1994 …