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 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.

Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning

“…This observation suggests that Fgf10 may serve as a mesenchyme factor for eyelid formation. Indeed, Fgf10 knockout embryos exhibit similar eyelid defects to those found in Fgfr2 ⌬III/⌬III mutant embryos (Min et al, 1998;Sekine et al, 1999). Fgf8 has been identified as a key factor in limb development; however, our in situ hybridization suggests that Fgf8 is unlikely to be essential for eyelid initiation as it is expressed at very low levels during early stages of eyelid development (data not shown).…”

The developmental basis of bat wing muscle

“…Furthermore, expression of the gene encoding the receptor of Fgf10, Fgfr2IIIb, was detected in the overlaying epidermis and some populations of the underlying mesenchyme of the wing membrane primordia and in the limb epidermis, including the AER. In vertebrates, maintenance of proximodistal outgrowth of the embryonic limbs requires Fgf10 in the mesenchyme to activate Fgf8 in the AER, which in turn promotes mesenchymal outgrowth 18,[34][35][36] . It appears that the outgrowths of the anterior, lateral and interfemoral wing membranes formed in bat embryos are achieved by a molecular mechanism that is partly different from that regulating the outgrowth of the limb.…”

Intercellular growth factor signaling and the development of mouse tracheal submucosal glands

“…In particular, it plays a key role in the distal lung, promoting outgrowth of epithelial buds (Bellusci et al, 1997;Min et al, 1998;Sekine et al, 1999;Weaver et al, 2000). We have found that in Fgf10 heterozygotes fewer SMGs are formed, and these do not undergo branching morphogenesis to their full extent.…”