Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless
Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless
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DOI：
10.1101/gad.12.20.3156
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发表时间：
1998-10-15
影响因子：
10.5
通讯作者：
Simonet, WS
中科院分区：
文献类型：
--
作者：
Min, HS;Danilenko, DM;Simonet, WS
建立成纤维细胞生长因子10基因缺陷小鼠(FGF10(-/-))，以确定FGF10在脊椎动物发育中的作用(S)。在成纤维细胞生长因子-10(-/-)小鼠中，肢芽启动被取消。引人注目的是，尽管完全没有前肢和后肢，但成纤维细胞生长因子-10(-/-)胎儿一直发育到出生。成纤维细胞生长因子-10是形成顶端外胚层脊(AER)所必需的，并且作用于成纤维细胞生长因子-8的上游，成纤维细胞生长因子-8是小鼠已知的最早的外胚层脊标记物。成纤维细胞生长因子-10(-/-)小鼠表现出与肺完全缺失相关的围产期死亡。虽然气管发育正常，但主干支气管的形成以及随后的所有肺分支形态发生完全中断。成纤维细胞生长因子-10(-/-)小鼠的肺表型与果蝇突变体Branchless惊人地相似，后者是成纤维细胞生长因子的同源物。
Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for apical ectodermal ridge (AER) formation and acts epistatically upstream of Fgf-8, the earliest known AER marker in mice. Fgf-10(-/-) mice exhibited perinatal lethality associated with complete absence of lungs. Although tracheal development was normal, main-stem bronchial formation, as well as all subsequent pulmonary branching morphogenesis, was completely disrupted. The pulmonary phenotype of Fgf-10(-/-) mice is strikingly similar to that of the Drosophila mutant branchless, an Fgf homolog.