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

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.