Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour

Nat Commun. 2019 Mar 12;10(1):1178. doi: 10.1038/s41467-019-09067-3.

Abstract

Damage to alveoli, the gas-exchanging region of the lungs, is a component of many chronic and acute lung diseases. In addition, insufficient generation of alveoli results in bronchopulmonary dysplasia, a disease of prematurity. Therefore visualising the process of alveolar development (alveologenesis) is critical for our understanding of lung homeostasis and for the development of treatments to repair and regenerate lung tissue. Here we show live alveologenesis, using long-term, time-lapse imaging of precision-cut lung slices. We reveal that during this process, epithelial cells are highly mobile and we identify specific cell behaviours that contribute to alveologenesis: cell clustering, hollowing and cell extension. Using the cytoskeleton inhibitors blebbistatin and cytochalasin D, we show that cell migration is a key driver of alveologenesis. This study reveals important novel information about lung biology and provides a new system in which to manipulate alveologenesis genetically and pharmacologically.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Actomyosin / antagonists & inhibitors
  • Actomyosin / physiology
  • Animals
  • Animals, Newborn
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cytochalasin D / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Intravital Microscopy
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Models, Animal
  • Organogenesis / drug effects
  • Organogenesis / physiology*
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / embryology*
  • Time-Lapse Imaging

Substances

  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin
  • Cytochalasin D
  • Actomyosin