Fgf10 is essential for limb and lung formation

  title={Fgf10 is essential for limb and lung formation},
  author={Keisuke Sekine and Hideyo Ohuchi and Masanori Fujiwara and Masahiro Yamasaki and Tatsuya Yoshizawa and Takashi Sato and Naoko Yagishita and Daisuke Matsui and Yoshihiko Koga and Nobuyuki Itoh and Shigeaki Kato},
  journal={Nature Genetics},
The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis. 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… 
The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth.
Normal limb development in conditional mutants of Fgf4.
Findings indicate that the previously proposed FGF4-SHH feedback loop is not essential for coordination of murine limb outgrowth and patterning and suggest that some of the roles currently attributed to F GF4 during early vertebrate limb development may be performed by other AER factors in vivo.
Identification of FGF10 Targets in the Embryonic Lung Epithelium during Bud Morphogenesis*
Global changes in gene expression are identified in lung epithelial explants undergoing FGF10-mediated budding in the absence of other growth factors and mesenchyme and found that some genes implicated in tumor invasion and metastatic behavior are epithelial targets of Fgf10 in the lung and other developing organs that depend on F gf10-Fgfr2 signaling to properly form.
Fibroblast Growth Factor 10 and Vertebrate Limb Development
The observed limb phenotype is similar to the severe proximal truncations observed in human babies exposed to thalidomide, which has been proposed to block the Fgf10-AER-Fgf8 feedback loop.
Fgf18 is required for embryonic lung alveolar development.
Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung.
Functions of FGF signalling from the apical ectodermal ridge in limb development
It is shown that FGF4 and FGF8 regulate cell number in the nascent limb bud and are required for survival of cells located far from the AER, and these functions are essential to ensure that sufficient progenitor cells are available to form the normal complement of skeletal elements, and perhaps other limb tissues.
Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.
A model for the combinatorial roles of Fgf10 and Bmp4 in branching morphogenesis of the lung is proposed and it is proposed that the Bmp-binding protein Noggin enhances F gf-induced morphogenesis.
FGF10 maintains distal lung bud epithelium and excessive signaling leads to progenitor state arrest, distalization, and goblet cell metaplasia
It is concluded that FGF 10 inhibits terminal differentiation in the embryonic lung and maintains the distal epithelium, and that excessive levels of FGF10 leads to metaplastic differentiation of goblet cells similar to that seen in chronic inflammatory diseases.
Requirements for FGF3 and FGF10 during inner ear formation
Double mutant mice are created for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for oic vesicle formation.


Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless.
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 Ff homolog.
Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung.
It is concluded that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.
The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor.
Evidence that a member of the fibroblast growth factor (FGF) family emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation is provided and results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.
Targeted expression of a dominant negative FGF receptor blocks branching morphogenesis and epithelial differentiation of the mouse lung.
To block the function ofFGFR2 during branching morphogenesis of the lung without affecting its function in other embryonic tissues, the human surfactant protein C promoter was used to target expression of a dominant negative FGFR2 exclusively to lung bud epithelium in transgenic mice.
Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis.
A role for Sonic hedgehog in lung morphogenesis is established, and it is suggested that SHH normally regulates lung mesenchymal cell proliferation in vivo.
Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction.
Findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction.
Sonic hedgehog regulates branching morphogenesis in the mammalian lung
The roles of FGFs in the early development of vertebrate limbs.
The purpose of this review is to discuss the functions performed by members of the FGF family in one of the best-studied vertebrate developmental systems—limb formation and discusses the potential role of FGFs in the induction of limb development.