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First published online 30 March 2005
doi: 10.1242/dev.01795

Development 132, 2157-2166 (2005)
Published by The Company of Biologists 2005
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Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage

Arnaud A. Mailleux1,*, Robert Kelly2, Jacqueline M. Veltmaat{dagger}, Stijn P. De Langhe3,{dagger}, Stephane Zaffran2, Jean Paul Thiery1 and Saverio Bellusci1,{dagger},{ddagger}

1 UMR144-CNRS/Institut Curie, 75248 Paris cedex 05, France
2 URA 2578 CNRS, Department of Developmental Biology, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France
3 Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB)-Ghent University, Technologiepark 927, B-9052 Ghent, Zwijnaarde, Belgium

{ddagger} Author for correspondence (e-mail: sbellusci{at}chla.usc.edu)

Accepted 27 February 2005

Lineage formation in the lung mesenchyme is poorly understood. Using a transgenic mouse line expressing LacZ under the control of Fgf10 regulatory sequences, we show that the pool of Fgf10-positive cells in the distal lung mesenchyme contains progenitors of the parabronchial smooth muscle cells. Fgf10 gene expression is slightly repressed in this transgenic line. This allowed us to create a hypomorphic Fgf10 phenotype by expressing the LacZ transgene in a heterozygous Fgf10 background. Hypomorphic Fgf10 mutant lungs display a decrease in ß-galactosidase-positive cells around the bronchial epithelium associated with an accumulation of ß-galactosidase-expressing cells in the distal mesenchyme. This correlates with a marked reduction of {alpha} smooth muscle actin expression, thereby demonstrating that FGF10 is mostly required for the entry of mesenchymal cells into the parabronchial smooth muscle cell lineage. The failure of exogenous FGF10 to phosphorylate its known downstream targets ERK and AKT in lung mesenchymal cultures strongly suggests that FGF10 acts indirectly on the progenitor population via an epithelial intermediate. We provide support for a role of epithelial BMP4 in mediating the formation of parabronchial smooth muscle cells.

Key words: Fgf10, Bmp4, Smooth muscle cells, Lung, Progenitors, Differentiation, Epithelial-mesenchymal interaction, Mouse




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