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Fgf10 is essential for limb and lung formation

Nature Genetics volume 21, pages 138–141 (1999)Cite this article

A Publisher Correction to this article was published on 04 April 2019

Abstract

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.

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Figure 1: Targeted disruption of the Fgf10 gene.
Figure 2: Skeletal malformation in Fgf10 mutant mice.
Figure 4: Absence of lung in Fgf10-/- mice.
Figure 3: Failure of induction of downstream genes of Fgf10 in the limb bud of Fgf10-/- embryos.
Figure 5: Morphology and gene expression in E11.

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Acknowledgements

We thank B.L.M. Hogan for critical reading and helpful discussion throughout this study; S. Noji and S. Bellusci for helpful discussion and advise; R. Yu for critical reading; V.E. Papaioannou, A. Tanaka, A. McMahon, T. Nohno and R.L. Johnson for cDNA probes; and S. Kume, Y. Yogiashi, K. Arioka, T. Kawakami and K. Takeyama for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Sports, Science and Culture of Japan (S.K.).

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan

    Keisuke Sekine, Tatsuya Yoshizawa, Takashi Sato, Naoko Yagishita, Daisuke Matsui & Shigeaki Kato

  2. Department of Genetic Biochemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan

    Hideyo Ohuchi, Masahiro Yamasaki & Nobuyuki Itoh

  3. Sumitomo Pharmaceuticals Research Center, Osaka, 554, Japan

    Masanori Fujiwara & Yoshihiko Koga

  4. CREST, Japan Science and Technology Corporation, Saitama, 332, Japan

    Shigeaki Kato

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  1. Keisuke Sekine
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Correspondence to Shigeaki Kato.

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Sekine, K., Ohuchi, H., Fujiwara, M. et al. Fgf10 is essential for limb and lung formation. Nat Genet 21, 138–141 (1999). https://doi.org/10.1038/5096

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