Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung.
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.
Abler
Lisa L
LL
Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Mansour
Suzanne L
SL
Sun
Xin
X
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008168:Lung / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology; D008648:Mesoderm / Q000196:embryology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000502:physiology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D017931:DNA Primers; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D055758:SOX9 Transcription Factor; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C527933:Sox9 protein, mouse; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2