Do lung remodeling, repair, and regeneration recapitulate respiratory ontogeny?

Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S59-62. doi: 10.1164/ajrccm.164.supplement_2.2106064.


Herein we posit that modeling of the lungs during morphogenesis, repair, and regeneration is tightly coordinated by conserved stimulatory and inhibitory signaling mechanisms, including specific transcriptional factors, cytokines, peptide growth factors, proteases, and matrix elements. This evolutionary-developmental (evo-devo) functional conservation has been extended to morphogenesis of the respiratory tracheae in Drosophila. Fifty or more genes direct fruit fly tracheal organogenesis. Among them, hedgehog, patched, smoothened, cubitus interruptus, branchless, breathless, sprouty, decapentaplegic, and mad are functionally conserved between flies, mice, and humans. For example, fibroblast growth factor (FGF) signaling is essential, not only for fly trachea and mouse bronchial branching morphogenesis, but also for postnatal modeling and repair of alveoli. Likewise, sprouty family genes act as inducible negative regulators of FGF signaling, which in part may determine interbranch length during bronchial development. Alveolar epithelial survival, migration, and proliferation during remodeling after hyperoxic injury also require FGF signaling. In addition, FGF signaling appears to regulate a small (< 5%) population of putative alveolar stem/ progenitor cells that express telomerase and are relatively resistant to hyperoxic apoptosis. We speculate that genes in evo-devo functionally conserved signaling pathways such as FGF-FGF receptor-Sprouty may provide novel therapeutic targets to augment lung repair and induce lung regeneration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Bronchi / embryology
  • Bronchopulmonary Dysplasia / genetics
  • Bronchopulmonary Dysplasia / pathology
  • Cell Movement
  • Cells, Cultured
  • Diptera / embryology
  • Diptera / genetics
  • Drosophila / embryology
  • Drosophila / genetics
  • Epitopes
  • Evolution, Molecular
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology*
  • Gestational Age
  • Humans
  • In Situ Hybridization
  • Infant, Newborn
  • Lung / embryology
  • Lung / physiology*
  • Mice
  • Morphogenesis*
  • Mutation
  • Phenotype
  • Pulmonary Alveoli / cytology
  • Rats
  • Regeneration*
  • Respiratory System / embryology*
  • Stem Cells / physiology
  • Trachea / embryology
  • Transcription Factors / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology


  • Epitopes
  • Transcription Factors
  • Transforming Growth Factor beta
  • Fibroblast Growth Factors