Fibroblast growth factor receptor 2-IIIb acts upstream of Shh and Fgf4 and is required for limb bud maintenance but not for the induction of Fgf8, Fgf10, Msx1, or Bmp4.
Developmental Biology. 2001-03-01; 231(1): 47-62
DOI: 10.1006/dbio.2000.0144
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Revest JM(1), Spencer-Dene B, Kerr K, De Moerlooze L, Rosewell I, Dickson C.
Author information:
(1)Imperial Cancer Research Fund, Lincoln’s Inn Fields, London, WC2A 3PX, United Kingdom
Mice deficient for FgfR2-IIIb were generated by placing translational stop
codons and an IRES-LacZ cassette into exon IIIb of FgfR2. Expression of the
alternatively spliced receptor isoform, FgfR2-IIIc, was not affected in mice
deficient for the IIIb isoform. FgfR2-IIIb(-/-) (lac)(Z) mice survive to term
but show dysgenesis of the kidneys, salivary glands, adrenal glands, thymus,
pancreas, skin, otic vesicles, glandular stomach, and hair follicles, and
agenesis of the lungs, anterior pituitary, thyroid, teeth, and limbs. Detailed
analysis of limb development revealed an essential role for FgfR2-IIIb in
maintaining the AER. Its absence did not prevent expression of Fgf8, Fgf10,
Bmp4, and Msx1, but did prevent induction of Shh and Fgf4, indicating that they
are downstream targets of FgfR2-IIIb activation. In the absence of FgfR2-IIIb,
extensive apoptosis of the limb bud ectoderm and mesenchyme occurs between E10
and E10.5, providing evidence that Fgfs act primarily as survival factors. We
propose that FgfR2-IIIb is not required for limb bud initiation, but is
essential for its maintenance and growth.