Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality

Abstract

Intrinsic cell chirality has been implicated in the left-right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels.

Epithelial Cell Chirality Revealed by Three-Dimensional Spontaneous Rotation

“…This platform is not intended to fully simulate in vivo environments for LR symmetry breaking, but it provides a simple yet effective system for determining chirality and thereby provides insight into possible regulatory mechanisms of LR asymmetry. We demonstrate that the direction of spontaneous rotation of both selforganized hollow cellular spheroids and individual epithelial cells residing at the interface of two layers of Matrigel is chiral in nature, with a CCW bias that is dependent on functional actin, consistent with the results from 2D ring patterning (16,28,29).…”

Cell chirality in cardiovascular development and disease

“…Patterned cells also demonstrate biases in the alignment of their nuclei and the direction of cell shape elongation. 64,65 Similar nuclear alignment was also observed by Huang et al using an outline etching image segmentation strategy. 60 Interestingly, inhibition of actin polymerization led to the reversal of the CCW chirality of C2C12 mouse myoblasts, supporting the role of the actin cytoskeleton in chirality development.…”

Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review

“…Hametner et al observed the elevation of iron accumulation with age increase in the white matter (WM) 1 . Iron-rich oligodendrocytes, myelin, and microglia were also destroyed in the active MS lesion, increasing the liberated iron, thereby intensifying oxidative damage and neurodegeneration 4 , 48 , 49 . Conversely, considerable reduction of iron and elevation of oxidative stress are found in MS patients 16 , 50 .…”

“…Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Its resultant inflammation causes oligodendrocyte degeneration, myelin sheath destruction, and neurodegeneration 1 – 4 . Although the origin of MS is still unknown, genetic predisposition and environmental toxicity activate the immune system against neural cells 5 , 6 .…”