Multiparametric image analysis of lung-branching morphogenesis

Dev Dyn. 2013 Jun;242(6):622-37. doi: 10.1002/dvdy.23961. Epub 2013 Apr 23.

Abstract

Background: Lung-branching morphogenesis is a fundamental developmental process, yet the cellular dynamics that occur during lung development and the molecular mechanisms underlying recent postulated branching modes are poorly understood.

Results: Here, we implemented a time-lapse video microscopy method to study the cellular behavior and molecular mechanisms of planar bifurcation and domain branching in lung explant- and organotypic cultures. Our analysis revealed morphologically distinct stages that are shaped at least in part by a combination of localized and orientated cell divisions and by local mechanical forces. We also identified myosin light-chain kinase as an important regulator of bud bifurcation, but not domain branching in lung explants.

Conclusions: This live imaging approach provides a method to study cellular behavior during lung-branching morphogenesis and suggests the importance of a mechanism primarily based on oriented cell proliferation and mechanical forces in forming and shaping the developing lung airways.

Publication types

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

MeSH terms

  • Animals
  • Cell Division
  • Cell Proliferation
  • Epithelium / embryology
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / metabolism
  • Image Processing, Computer-Assisted
  • Lung / embryology*
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Microscopy, Video*
  • Morphogenesis*
  • Myosin-Light-Chain Kinase / metabolism
  • Promoter Regions, Genetic
  • Stress, Mechanical
  • Time Factors

Substances

  • Green Fluorescent Proteins
  • Myosin-Light-Chain Kinase