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1: Development. 2006 Apr;133(8):1507-17. Epub 2006 Mar 15.

FGF9 and SHH signaling coordinate lung growth and development through regulation 
of distinct mesenchymal domains.

White AC, Xu J, Yin Y, Smith C, Schmid G, Ornitz DM.

Department of Molecular Biology and Pharmacology, Washington University Medical
School, St Louis, MO 63110, USA.

Morphogenesis of the lung is regulated by reciprocal signaling between epithelium
and mesenchyme. In previous studies, we have shown that FGF9 signals are
essential for lung mesenchyme development. Using Fgf9 loss-of-function and
inducible gain-of-function mouse models, we show that lung mesenchyme can be
divided into two distinct regions: the sub-mesothelial and sub-epithelial
compartments, which proliferate in response to unique growth factor signals.
Fibroblast growth factor (FGF) 9 signals from the mesothelium (the future pleura)
to sub-mesothelial mesenchyme through both FGF receptor (FGFR) 1 and FGFR2 to
induce proliferation. FGF9 also signals from the epithelium to the sub-epithelial
mesenchyme to maintain SHH signaling, which regulates cell proliferation,
survival and the expression of mesenchymal to epithelial signals. We further show
that FGF9 represses peribronchiolar smooth muscle differentiation and stimulates 
vascular development in vivo. We propose a model in which FGF9 and SHH signals
cooperate to regulate mesenchymal proliferation in distinct submesothelial and
subepithelial regions. These data provide a molecular mechanism by which
mesothelial and epithelial FGF9 directs lung development by regulating
mesenchymal growth, and the pattern and expression levels of mesenchymal growth
factors that signal back to the epithelium.

PMID: 16540513 [PubMed - indexed for MEDLINE]

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