Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality
- 344 Downloads
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.
KeywordsCell chirality Cell polarity Cell morphology Nuclear morphology
The authors thank Parker Haynes for his help on Python coding. The authors would like to thank National Institutes of Health, National Science Foundation, American Heart Association, and March of Dimes for funding Support. Leo Q. Wan is a Pew Scholar in Biomedical Sciences, supported by the Pew Charitable Trusts.
Conflict of interest
All authors, Michael J. Raymond, Poulomi Ray, Gurleen Kaur, Michael Fredericks, Ajay V. Singh, and Leo Q. Wan, declare that they have no conflict of interest.
Statements of Human and Animal Rights and Informed Consent
No human or animal research was conducted in this study.
- 3.Balcarova-Stander, J., S. E. Pfeiffer, S. D. Fuller, and K. Simons. Development of cell surface polarity in the epithelial Madin–Darby canine kidney (MDCK) cell line. EMBO J. 3:2687–2694, 1984.Google Scholar
- 15.Johnson-Leger, C., M. Aurrand-Lions, and B. A. Imhof. The parting of the endothelium: miracle, or simply a junctional affair? J. Cell Sci. 113:921–933, 2000.Google Scholar
- 20.Kvietys, P. R., and M. Sandig. Neutrophil diapedesis: paracellular or transcellular? News Physiol. Sci. 16:15–19, 2001.Google Scholar
- 43.Wagner, J. G., and R. A. Roth. Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol. Rev. 52:349–374, 2000.Google Scholar