Murine FGFR-1 is required for early postimplantation growth and axial organization.
We have explored the role of fibroblast growth factor receptor 1 (FGFR-1) in early embryonic development using three experimental systems: genetically deficient mice, in vitro blastocyst culture, and FGFR-1-deficient 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 gastrulation. Although these mutants can form nonaxial tissues, such as the allantois, amnion, and yolk sac mesoderm, they display defective patterning of the primitive streak and other axial structures, and frequently exhibit truncations or disorganization of posterior embryonic regions. 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.
Deng
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CX
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115.
Wynshaw-Boris
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A
Shen
M M
MM
Daugherty
C
C
Ornitz
D M
DM
Leder
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P
D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000502:physiology*; D002454:Cell Differentiation; D017931:DNA Primers; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005091:Exons; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000502:physiology; D005822:Genetic Vectors; D005838:Genotype; D006720:Homozygote; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015183:Restriction Mapping; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014981:Xenopus
D017931:DNA Primers; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1