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

TLDR

Fgf‑10 is essential for apical ectodermal ridge formation and functions upstream of Fgf‑8 in mouse limb development. The study generated Fgf‑10 knockout mice to investigate Fgf‑10’s role in vertebrate development. Fgf‑10 knockout mice lack limb bud initiation and lung development, survive to birth without limbs, exhibit perinatal lethality, and display a bronchial branching defect analogous to the Drosophila branchless mutant.

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 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.