FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains
Open Access
- 15 April 2006
- journal article
- Published by The Company of Biologists in Development
- Vol. 133 (8), 1507-1517
- https://doi.org/10.1242/dev.02313
Abstract
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.Keywords
This publication has 44 references indexed in Scilit:
- Fgf10expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineageDevelopment, 2005
- Distal angiogenesis: a new concept for lung vascular morphogenesisAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Epithelial-Mesenchymal Interactions in the Developing LungAnnual Review of Physiology, 2004
- Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lungGenes & Development, 2003
- Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathwayNature, 2002
- Hedgehog signaling in animal development: paradigms and principlesGenes & Development, 2001
- Noggin, Cartilage Morphogenesis, and Joint Formation in the Mammalian SkeletonScience, 1998
- Receptor Specificity of the Fibroblast Growth Factor FamilyJournal of Biological Chemistry, 1996
- Keratinocyte growth factor is required for hair development but not for wound healing.Genes & Development, 1996
- Expression and Biological Activity of Mouse Fibroblast Growth Factor-9Published by Elsevier BV ,1996