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

Full Abstract

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. Copyright (c) 2009 Wiley-Liss, Inc.

Author information

Author/s: Abler, Lisa L (LL); Mansour, Suzanne L (SL); Sun, Xin (X);

Affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Grants: R01DC004185 (Agency:NIDCD NIH HHS) ; R01DC005608 (Agency:NIDCD NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Developmental dynamics : an official publication of the American Association of Anatomists (Dev Dyn), published in United States. (Language: eng)

Reference: 2009-Aug; vol 238 (issue 8) : pp 1999-2013

Dates: Created 2009/08/03; Completed 2009/11/16;

PMID: 19618463, status: MEDLINE (last retrieved date: 11/16/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Base Sequence
Body Patterning - genetics; physiology
Cell Death - genetics; physiology
Cell Survival - genetics; physiology
DNA Primers - genetics
Epithelium - embryology; physiology
Female
Fibroblast Growth Factor 10 - deficiency; genetics; physiology
Gene Expression Regulation, Developmental
Gene Targeting

Lung - abnormalities; embryology; physiology
Mesoderm - embryology; physiology
Mice
Mice, Knockout
Mice, Mutant Strains
Mice, Transgenic
Pregnancy
Receptor, Fibroblast Growth Factor, Type 2 - deficiency; genetics; physiology
SOX9 Transcription Factor - genetics; physiology
SOXB1 Transcription Factors - genetics; physiology
Signal Transduction

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: DNA Primers (0) ; Fgf10 protein, mouse (0) ; Fibroblast Growth Factor 10 (0) ; SOX9 Transcription Factor (0) ; SOXB1 Transcription Factors (0) ; Sox2 protein, mouse (0) ; Sox9 protein, mouse (0) ; Fgfr2 protein, mouse (EC 2.7.1.112) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.1.112)

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