Abstract
ABSTRACTDuring 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.This article has an associated ‘The people behind the papers’ interview.
Highlights
Epithelial tubes are an essential component of many organs
We combined a quantitative analysis of lung and kidney branching morphogenesis with computational modelling to evaluate candidate mechanisms for the biased elongation of epithelial tubes
We show that biased elongation is an inherent property of these epithelial tubes, and that it does not require contact with the mesenchyme or an external chemotactic gradient
Summary
Epithelial tubes are an essential component of many organs. During development, epithelial tubes elongate (Fig. 1A). Branch shape is normal when Mylk, which encodes myosin light chain kinase (MLCK), an essential factor for ASM contraction, is inactivated during lung development (Young et al, 2020). This suggests that ASM cells may affect tube diameter via nonmechanical cues. We sought to systematically analyse the minimal requirements for biased epithelial tube elongation To this end, we cultured mouse embryonic lungs and kidneys under different conditions and quantified the length and width of the branches for up to 60 h. A cell-based model confirms that a tangential apical force, as provided by shear stress, can result in the reported bias in cell shape and elongating outgrowth
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