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PMID:9435295

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Citation

Xu, X, Weinstein, M, Li, C, Naski, M, Cohen, RI, Ornitz, DM, Leder, P and Deng, C (1998) Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125:753-65

Abstract

FGFR2 is a membrane-spanning tyrosine kinase that serves as a high affinity receptor for several members of the fibroblast growth factor (FGF) family. To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor. We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation. Fgfr2(DeltaIgIII/DeltaIgIII) embryos displayed two distinct defects that resulted in failures in formation of a functional placenta. About one third of the mutants failed to form the chorioallantoic fusion junction and the remaining mutants did not have the labyrinthine portion of the placenta. Consequently, all mutants died at 10-11 days of gestation. Interestingly, Fgfr2(DeltaIgIII/DeltaIgIII) embryos do not form limb buds. Consistent with this defect, the expression of Fgf8, an apical ectodermal factor, is absent in the mutant presumptive limb ectoderm, and the expression of Fgf10, a mesenchymally expressed limb bud initiator, is down regulated in the underlying mesoderm. These findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction.

Links

PubMed

Keywords

Animals; Base Sequence; DNA Primers/genetics; Ear, Inner/embryology; Embryonic Induction/genetics; Extremities/embryology; Female; Fibroblast Growth Factor 10; Fibroblast Growth Factor 8; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/physiology; Gene Expression Regulation, Developmental; Growth Substances/genetics; Growth Substances/physiology; Male; Mice; Mice, Knockout; Mutation; Phenotype; Placentation/genetics; Placentation/physiology; Polymerase Chain Reaction; Pregnancy; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/physiology; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor/genetics; Receptors, Fibroblast Growth Factor/physiology; Sequence Deletion; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FGF8

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0001701: in utero embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0040014: regulation of multicellular organism growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0030916: otic vesicle formation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0060174: limb bud formation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete

MOUSE:FGFR2

enables

GO:0017134: fibroblast growth factor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0048568: embryonic organ development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0060670: branching involved in labyrinthine layer morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153790

P

Seeded From UniProt

complete


See also

References

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