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1: Dev Biol. 2006 May 1;293(1):77-89. Epub 2006 Feb 21.

Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung.

del Moral PM, De Langhe SP, Sala FG, Veltmaat JM, Tefft D, Wang K, Warburton D,
Bellusci S.

Developmental Biology Program, Saban Research Institute of Children's Hospital
Los Angeles, Los Angeles, CA 90027, USA.

Mesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by
inactivation studies in mouse to be critical for the proliferation of the
mesenchyme. We now show that Fgf9 is also expressed at significant levels in the 
distal epithelium from the mid-pseudoglandular stages. Using mesenchymal-free
lung endoderm culture, we show that FGF9 triggers the proliferation of the distal
epithelium leading to the formation of a cyst-like structure. On embryonic
Fgfr2b-/- lungs, FGF9 induces proliferation of the mesenchyme but fails to
trigger a similar effect on the epithelium, therefore involving the FGFR2b
receptor in the proliferative response of the epithelium to FGF9. While FGF9
inhibits the differentiation of the mesenchyme, the epithelium appears to
differentiate normally. At the molecular level, FGF9 up-regulates Fgf10
expression in the mesenchyme likely via increased expression of Tbx4 and 5 and
controls the transcription of Hedgehog targets Ptc and Gli-1 in a
Hedgehog-independent manner. We also show that FGF9 inhibits the activation of
the canonical Wnt pathway in the epithelium by increasing Dkk1 expression, a
canonical Wnt antagonist. Our work shows for the first time that FGF9 acts on the
epithelium involving FGFR2b to control its proliferation but not its
differentiation and contributes to the regulation of canonical Wnt signaling in
the epithelium.

PMID: 16494859 [PubMed - indexed for MEDLINE]

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