Fibroblast growth factor 9 signaling inhibits airway smooth muscle differentiation in mouse lung

Dev Dyn. 2009 Jan;238(1):123-37. doi: 10.1002/dvdy.21831.

Abstract

In mammalian lungs, airway smooth muscle cells (airway SMCs) are present in the proximal lung adjacent to bronchi and bronchioles, but are absent in the distal lung adjacent to terminal sacs that expand during gas exchange. Evidence suggests that this distribution is essential for the formation of a functional respiratory tree, but the underlying genetic mechanism has not been elucidated. In this study, we test the hypothesis that fibroblast growth factor 9 (Fgf9) signaling is essential to restrict SMC differentiation to the proximal lung. We show that loss of Fgf9 or conditional inactivation of Fgf receptors (Fgfr) 1 and 2 in mouse lung mesenchyme results in ectopic SMCs. Our data support a model where FGF9 maintains a SMC progenitor population by suppressing differentiation and promoting growth. This model also represents our findings on the genetic relationship between FGF9 and sonic hedgehog (SHH) in the establishment of airway SMC pattern.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Differentiation / physiology*
  • Female
  • Fibroblast Growth Factor 9 / genetics
  • Fibroblast Growth Factor 9 / metabolism*
  • Lung* / anatomy & histology
  • Lung* / metabolism
  • Male
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Carrier Proteins
  • Fibroblast Growth Factor 9
  • Nuclear Proteins
  • Trans-Activators
  • myocardin
  • noggin protein
  • Fgfr1 protein, mouse
  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2