The biomechanical basis of biased epithelial tube elongation in lung and kidney development
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Date
2021-05
Publication Type
Journal Article
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yes
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Abstract
During lung development, epithelial branches expand preferentially in a longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How this bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme, of preferential turnover of the extracellular matrix at the bud tips and of FGF signalling. There is also no evidence for actin-rich filopodia at the bud tips. Rather, we find epithelial tubes to be collapsed during early lung and kidney development, and we observe fluid flow in the narrow tubes. By simulating the measured fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis.
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published
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Journal / series
Volume
148 (9)
Pages / Article No.
Publisher
Company of Biologists
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Edition / version
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Date collected
Date created
Subject
Epithelial tube; Directional growth; Light-sheet imaging; Computational model; Shear stress; Cell-based tissue simulations
Organisational unit
03791 - Iber, Dagmar / Iber, Dagmar
Notes
Funding
170930 - A 3D Cell-Based Simulation Framework for Morphogenetic Problems (SNF)
Related publications and datasets
Is new version of: http://hdl.handle.net/20.500.11850/444723