Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless

Abstract

Fgf-10-deficient mice (Fgf-10^−/− ) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished inFgf-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 ofFgf-10^−/− mice is strikingly similar to that of the Drosophila mutant branchless, anFgf homolog.