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Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour
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Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour
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Journal Article
Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour
2019
Overview
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.
The process of alveologenesis is incompletely understood, partly due to the lack of applicable real-time imaging methods. Here the authors describe the process of alveologenesis and the behaviour of epithelial cells in real-time, using widefield microscopy and image deconvolution in precision-cut lung slices, revealing the dominant role of epithelial cell migration.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/1
/ 14/19
/ Actomyosin - antagonists & inhibitors
/ Alveoli
/ Animals
/ Cell Movement - drug effects
/ Cytochalasin D - pharmacology
/ Epithelial Cells - drug effects
/ Epithelial Cells - physiology
/ Heterocyclic Compounds, 4 or More Rings - pharmacology
/ Humanities and Social Sciences
/ Lungs
/ Mice
/ Organogenesis - drug effects
/ Pulmonary Alveoli - drug effects
/ Pulmonary Alveoli - embryology
/ Science
