MURINE FGFR-1 IS REQUIRED FOR EARLY POSTIMPLANTATION GROWTH AND AXIALORGANIZATION

We have explored the role of fibroblast growth factor receptor 1 (FGFR -1) in early embryonic development using three experimental systems: g enetically deficient mice, in vitro blastocyst culture, and FGFR-1-def icient embryonic stem cells. Using these systems, we demonstrate that FGFR-1 is required for proper embryonic cell proliferation and for the correct axial organization of early postimplantation embryos but not for mesoderm formation. FGFR-1-deficient embryos display severe growth retardation both in vitro and in vivo and die prior to or during gast rulation. Although these mutants can form nonaxial tissues, such as th e allantois, amnion, and yolk sac mesoderm, they display defective pat terning of the primitive streak and other axial structures, and freque ntly exhibit truncations or disorganization of posterior embryonic reg ions. Such abnormalities are unlikely to be caused by intrinsic blocks in mesodermal differentiation, as FGFR-1-deficient ES cell lines form teratomas consisting of many mesodermal cell types.