Min H, Danilenko D M, Scully S A, Bolon B, Ring B D, Tarpley J E, DeRose M, Simonet W S
Department of Molecular Genetics, Amgen, Inc., Thousand Oaks, California 91320-1789 USA.
Genes Dev. 1998 Oct 15;12(20):3156-61. doi: 10.1101/gad.12.20.3156.
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.
为了确定Fgf-10在脊椎动物发育中的作用，构建了Fgf-10基因敲除小鼠（Fgf-10(-/-)）。在Fgf-10(-/-)小鼠中，肢芽起始被消除。令人惊讶的是，尽管完全没有前肢和后肢，Fgf-10(-/-)胎儿仍能继续发育直至出生。Fgf-10对于顶端外胚层嵴（AER）的形成是必需的，并且在Fgf-8（小鼠中最早已知的AER标记物）的上游发挥上位性作用。Fgf-10(-/-)小鼠表现出与完全没有肺相关的围产期致死性。尽管气管发育正常，但主支气管形成以及所有后续的肺分支形态发生都完全被破坏。Fgf-10(-/-)小鼠的肺表型与果蝇突变体branchless（一种Fgf同源物）的表型惊人地相似。
