Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung

• Published in: Developmental dynamics 2009-08, Vol.238 (8), p.1999-2013
• Main Authors: Abler, Lisa L., Mansour, Suzanne L., Sun, Xin
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Body Patterning - genetics; Body Patterning - physiology; branching morphogenesis; Cell Death - genetics; Cell Death - physiology; cell survival; Cell Survival - genetics; Cell Survival - physiology; development; DNA Primers - genetics; Epithelium - embryology; Epithelium - physiology; Female; Fgf10; Fgfr2; Fibroblast Growth Factor 10 - deficiency; Fibroblast Growth Factor 10 - genetics; Fibroblast Growth Factor 10 - physiology; Gene Expression Regulation, Developmental; Gene Targeting; lung; Lung - abnormalities; Lung - embryology; Lung - physiology; Mesoderm - embryology; Mesoderm - physiology; Mice; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Pregnancy; proximal–distal patterning; Receptor, Fibroblast Growth Factor, Type 2 - deficiency; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 2 - physiology; Signal Transduction; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - physiology; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - physiology
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.22032

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.