title: Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage.
abstract: 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 beta-galactosidase-positive cells around the bronchial epithelium associated with an accumulation of beta-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.
authors.affiliation: UMR144-CNRS/Institut Curie, 75248 Paris cedex 05, France.
authors.forename: Arnaud A
authors.initials: AA
authors.lastname: Mailleux
authors.forename: Robert
authors.initials: R
authors.lastname: Kelly
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Veltmaat
authors.forename: Stijn P
authors.initials: SP
authors.lastname: De Langhe
authors.forename: Stephane
authors.initials: S
authors.lastname: Zaffran
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: Saverio
authors.initials: S
authors.lastname: Bellusci
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001980:Bronchi / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D032390:Myoblasts, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000199:Actins; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors