Lung development and repair: contribution of the ciliated lineage

Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):410-7. doi: 10.1073/pnas.0610770104. Epub 2006 Dec 28.

Abstract

The identity of the endogenous epithelial cells in the adult lung that are responsible for normal turnover and repair after injury is still controversial. In part, this is due to a paucity of highly specific genetic lineage tools to follow efficiently the fate of the major epithelial cell populations: the basal, secretory, ciliated, neuroendocrine, and alveolar cells. As part of a program to address this problem we have used a 1-kb FOXJ1 promoter to drive CreER in the ciliated cells of the embryonic and adult lung. Analysis of FOXJ1-GFP transgenic lungs shows that labeled cells appear in a proximal-distal pattern during embryogenesis and that the promoter drives expression in all ciliated cells. Using FOXJ1CreER adult mice, we have followed the fate of ciliated cells after epithelial injury by naphthalene or sulfur dioxide. From quantitative analysis and confocal microscopy we conclude that ciliated cells transiently change their morphology in response to lung injury but do not proliferate or transdifferentiate as part of the repair process.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cilia / metabolism
  • Cilia / ultrastructure*
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Humans
  • Lung / drug effects
  • Lung / embryology*
  • Lung / growth & development*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Naphthalenes / toxicity
  • Promoter Regions, Genetic
  • Recombinant Proteins / genetics
  • Sulfur Dioxide / toxicity
  • Wound Healing

Substances

  • FOXJ1 protein, human
  • Forkhead Transcription Factors
  • Naphthalenes
  • Recombinant Proteins
  • Sulfur Dioxide
  • Green Fluorescent Proteins
  • naphthalene