Fgf10 is essential for limb and lung formation
Keisuke Sekine, Hideyo Ohuchi, Masanori Fujiwara, Masahiro Yamasaki, Tatsuya Yoshizawa, Takashi Sato, Naoko Yagishita, Daisuke Matsui, Yoshihiko Koga, Nobuyuki Itoh & Shigeaki Kato
nature genetics volume 21 january 1999 (free pdf)
The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis1,2. In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10−/−mice died at birth due to the lack of lung development. Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10–/–embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.
Fig. 2 Skeletal malformation in Fgf10mutant mice. Newborn Fgf10+/- (left) and Fgf10–/–pups from side (a) and frontal (b) views. Skeletal structure of heterozygous (c) and homozygous (d) mutant pups stained with alizarin red and alcian blue is shown. The phenotype of the scapula in Fgf10+/–(e)and Fgf10−/− pups (f) is shown, as well as the phenotype of the clavicle in Fgf10+/–(g) and Fgf10−/−pups (h). Phenotype of the hindlimb is shown in side (i,j) and frontal (k,l) views. A rudimentary pelvis is seen, but hindlimb components such as digits, fibula, tibia and femur are absent in homozygotes (j,l) compared with heterozygous pups (i,k). H, humerus; U, ulna; R, radius; Fe, femur; Fi, fibula; T, tibia; S, scapula; C, clavicle; Il, ilium; Is, ischium; P, pubis.
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