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
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
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DOI：
10.1006/dbio.2000.0144
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发表时间：
2001-03-01
影响因子：
2.7
通讯作者：
Dickson, C
中科院分区：
文献类型：
--
作者：
Revest, JM;Spencer-Dene, B;Dickson, C
通过将翻译终止密码子和IRES-LacZ盒置于FgfR 2的外显子IIIb中产生FgfR 2-IIIb缺陷小鼠。选择性剪接受体亚型FgfR 2-IIIc的表达在IIIb亚型缺陷的小鼠中不受影响。FgfR 2-IIIb（-/-）（lacZ）小鼠存活至足月，但显示肾脏、唾液腺、肾上腺、胸腺、胰腺、皮肤、耳泡、腺胃和毛囊发育不全，以及肺、垂体前叶、甲状腺、牙齿和四肢发育不全。肢体发育的详细分析揭示了FgfR 2-IIIb在维持AER中的重要作用。它的缺失并不阻止Fgf 8、Fgf 10、Bmp 4和Msx 1的表达，但确实阻止了Shh和Fgf 4的诱导，表明它们是FgfR 2-IIIb激活的下游靶点。在FgfR 2-IIIb的情况下，肢芽外胚层和间充质的广泛凋亡发生在E10和E10.5之间，提供了Fgfs主要作为存活因子的证据。我们认为FgfR 2-IIIb不是肢芽形成所必需的，但对肢芽的维持和生长至关重要。(C)北京：科学出版社.
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(-/-) (lacZ) 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. (C) 2001 Academic Press.