Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless.
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.
Min
H
H
Department of Molecular Genetics, Amgen, Inc., Thousand Oaks, California 91320-1789 USA.
Danilenko
D M
DM
Scully
S A
SA
Bolon
B
B
Ring
B D
BD
Tarpley
J E
JE
DeRose
M
M
Simonet
W S
WS
D000818:Animals; D000831:Animals, Newborn / Q000002:abnormalities; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D005804:Genes, Lethal; D019476:Insect Proteins / Q000502:physiology*; D017880:Limb Deformities, Congenital / Q000196:embryology / Q000235:genetics*; D008168:Lung / Q000002:abnormalities*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype
D029721:Drosophila Proteins; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D019476:Insect Proteins; C102644:bnl protein, Drosophila; D005346:Fibroblast Growth Factors