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

• Published in: Nature communications 2018-06, Vol.9 (1), p.2161-15, Article 2161
• Main Authors: Merks, Anne Margarete, Swinarski, Marie, Meyer, Alexander Matthias, Müller, Nicola Victoria, Özcan, Ismail, Donat, Stefan, Burger, Alexa, Gilbert, Stephen, Mosimann, Christian, Abdelilah-Seyfried, Salim, Panáková, Daniela
• Format: Article
• Language: English
• Subjects: 13/1; 14/19; 631/136; 631/136/1660; 64; 64/116; Actomyosin; Actomyosin - genetics; Actomyosin - metabolism; Animals; Animals, Genetically Modified; Atrial Remodeling - genetics; Cardiomyocytes; Cell Polarity - genetics; Cell Polarity - physiology; Embryonic Development - genetics; Heart; Heart - embryology; Heart diseases; Humanities and Social Sciences; Ligands; Membranes; Molecular chains; Morphology; multidisciplinary; Muscle contraction; Mutation; Myocardium - cytology; Myocardium - metabolism; Physiology; Polarity; Polarization; Science; Science (multidisciplinary); Signal Transduction; Signaling; Tension; Ventricular Remodeling - genetics; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt-5a Protein - genetics; Wnt-5a Protein - metabolism; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04566-1

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. The molecular mechanisms underlying cardiac chamber formation are not well understood. Here, the authors show that planar cell polarity signalling through Wnt5b and Wnt11 coordinates localised and tissue-scale polarised actomyosin contractility in the zebrafish heart, regulating cardiac chamber formation and looping.