Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung
Version of Record online: 17 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
Volume 238, Issue 8, pages 1999–2013, August 2009
How to Cite
Abler, L. L., Mansour, S. L. and Sun, X. (2009), Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung. Dev. Dyn., 238: 1999–2013. doi: 10.1002/dvdy.22032
- Issue online: 17 JUL 2009
- Version of Record online: 17 JUL 2009
- Manuscript Accepted: 29 MAY 2009
- Burroughs-Wellcome. Grant Number: Career award 1002361
- University of Wisconsin Medical Education Research Committee. Grant Numbers: Young Investigator Award, R01DC005608, R01DC004185
- branching morphogenesis;
- cell survival;
- proximal–distal patterning
Fibroblast growth factor 10 (FGF10) signaling through FGF receptor 2 (FGFR2) is required for lung initiation. While studies indicate that Fgf10 and Fgfr2 are also important at later stages of lung development, their roles in early branching events remain unclear. We addressed this question through conditional inactivation of both genes in mouse subsequent to lung initiation. Inactivation of Fgf10 in lung mesenchyme resulted in smaller lobes with a reduced number of branches. Inactivation of Fgfr2 in lung epithelium resulted in disruption of lobes and small epithelial outgrowths that arose arbitrarily along the main bronchi. In both mutants, there was an increase in cell death. Also, the expression patterns of key signaling molecules implicated in branching morphogenesis were altered and a proximal lung marker was expanded distally. Our results indicate that both Fgf10 and Fgfr2 are required for a normal branching program and for proper proximal–distal patterning of the lung.Developmental Dynamics 238:1999–2013, 2009. © 2009 Wiley-Liss, Inc.