Fgf10 is essential for limb and lung formation

Fgf10 is essential for limb and lung formation
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DOI:
10.1038/5096
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发表时间:
1999-01-01
期刊:
影响因子:
30.8
通讯作者:
Kato, S
Kato, S
中科院分区:
生物学1区
文献类型:
--
作者:
Sekine, K;Ohuchi, H;Kato, S

文献摘要

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成纤维细胞生长因子(FGF)及其受体之间的相互作用在胚胎发生期间介导间充质-上皮细胞相互作用中具有重要作用(1,2)。特别地,预测Fgf 10作为脑、肺和肢体发育的调节剂起作用,这是其在发育中的胚胎中的时空表达模式的基础。为了确定Fgf 10的作用,我们产生了Fgf 10缺陷小鼠。Fgf 10(-/-)小鼠出生时因肺部发育不足而死亡,形成了气管,但随后的肺部分支形态发生被破坏。此外,突变小鼠的前肢和后肢完全截断。在Fgf 10(-/-)胚胎中,肢芽形成开始,但肢芽的生长没有发生;然而,锁骨的形成不受影响。对突变体肢芽中标记基因表达的分析表明,顶端外胚层嵴(AER)和极化活性音调(ZPA)没有形成。因此,我们在这里表明,FGF 10作为肺和肢体形成的重要调节因子。
The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis(1,2). In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development an the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10(-/-) mice died at birth due to the lack of lung development Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10(-/-) embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the tone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.