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.
Highlights
Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping
We focused on the outflow tract (OFT) region as ventricular chamber expansion depends on the accrual of cells from the second heart field (SHF)-derived pool of cardiac progenitors through the arterial pole, and we observed that the mean angle of the OFT cardiomyocyte orientation in wild-type hearts is 92.27° with low distribution (Fig. 1c)
Discussion the molecular signature governing the formation of the vertebrate cardiac chambers has been studied in great detail[3,10], the cellular processes underlying the remodelling of the linear heart tube (LHT) into its chambered form remain enigmatic
Summary
Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. This regional increase in cell size[7,8] and the subsequent differential hypertrophic growth has been demonstrated experimentally and by computational modelling to be the driving force behind cardiac looping and chamber ballooning[7,9] The consequence of these complex morphogenetic processes is the emergence of the atrio-ventricular junction (AVJ), and the formation of the atrium and the ventricle that in zebrafish acquire characteristic bean-like shape morphology with inner (IC) and convex outer curvatures (OC). Detailed retrospective clonal analysis in the mouse has revealed that the expansion of cardiac chambers is coordinated through oriented clonal growth consistent with the left ventricle bulging from the outer curvature of the LHT11 Both the underlying signalling and the cellular mechanisms that drive the chamber formation and the LHT remodelling remain unclear. Wnt non-canonical ligands and all core PCP components are expressed in the heart[21,22,23,24,25], and mutations in several pathway components lead to congenital heart disease associated with defects in outflow tract remodelling[26], the precise role of PCP during cardiogenesis remains incompletely understood
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