Planar cell polarity signalling coordinates heart tube remodelling through tissue-scale polarisation of actomyosin activity

平面细胞极性信号通过组织尺度肌动球蛋白活性极化来协调心管重塑

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作者:Anne Margarete Merks, Marie Swinarski, Alexander Matthias Meyer, Nicola Victoria Müller, Ismail Özcan, Stefan Donat, Alexa Burger, Stephen Gilbert, Christian Mosimann, Salim Abdelilah-Seyfried, Daniela Panáková

Abstract

Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange. On a tissue-scale, PCP signalling planar-polarises tissue tension by restricting the actomyosin contractility to the apical membranes of outflow tract cells. The tissue-scale polarisation of actomyosin contractility is required for cardiac looping that occurs concurrently with chamber ballooning. Taken together, our data reveal that instructive PCP signals couple cardiac chamber expansion with cardiac looping through the organ-scale polarisation of actomyosin-based tissue tension.

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