Quantitative analysis of polarity in 3D reveals local cell coordination in the embryonic mouse heart

Abstract

Anisotropies that underlie organ morphogenesis have been quantified in 2D, taking advantage of a reference axis. However, morphogenesis is a 3D process and it remains a challenge to analyze cell polarities in 3D. Here, we have designed a novel procedure that integrates multidisciplinary tools, including image segmentation, statistical analyses, axial clustering and correlation analysis. The result is a sensitive and unbiased assessment of the significant alignment of cell orientations in 3D, compared with a random axial distribution. Taking the mouse heart as a model, we validate the procedure at the fetal stage, when cardiomyocytes are known to be aligned. At the embryonic stage, our study reveals that ventricular cells are already coordinated locally. The centrosome-nucleus axes and the cell division axes are biased in a plane parallel to the outer surface of the heart, with a minor transmural component. We show further alignment of these axes locally in the plane of the heart surface. Our method is generally applicable to other sets of vectors or axes in 3D tissues to map the regions where they show significant alignment.

Single-Cell Lineage Tracing Reveals that Oriented Cell Division Contributes to Trabecular Morphogenesis and Regional Specification

“…Previous work showed that cardiomyocytes at E13.5 undergo primarily parallel OCD based on IFS (Le Garrec et al, 2013), which is consistent with the heart morphogenesis at E13.5, a stage in which trabecular formation is already completed and the heart undergoes expansion. Hence, a high percentage of parallel OCD would be expected.…”

Atypical Protein Kinase C-Dependent Polarized Cell Division Is Required for Myocardial Trabeculation

“…Previously Le Garrec et al demonstrated that myocardial cell division is oriented with a planar bias in embryonic mouse hearts (Le Garrec et al, 2013). We therefore examined E8.5 embryos (prior to the onset of trabeculation) to determine whether luminal myocardial cells displayed oriented cell division relative to the axis of polarity defined by the heart lumen.…”

A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

“…It is tempting to speculate that regional polarization of cardiomyoctes combined with specific coordinated movement of regionalized cells results in organ-intrinsic heart looping. Corroborating such a mechanism are recent studies demonstrating that various cell lines exhibit intrinsic left-right polarity 33,34,44 , whereas elegant imaging analyses have demonstrated regionalized cell polarity coordination in the mouse heart during development 45 .…”