Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives

Yee Han Tee (), Wei Jia Goh, Xianbin Yong, Hui Ting Ong, Jinrong Hu, Ignacius Yan Yun Tay, Shidong Shi, Salma Jalal, Samuel F. H. Barnett, Pakorn Kanchanawong, Wenmao Huang, Jie Yan, Yong Ann Ben Lim, Visalatchi Thiagarajan, Alex Mogilner and Alexander D. Bershadsky ()
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Yee Han Tee: National University of Singapore
Wei Jia Goh: National University of Singapore
Xianbin Yong: National University of Singapore
Hui Ting Ong: National University of Singapore
Jinrong Hu: National University of Singapore
Ignacius Yan Yun Tay: National University of Singapore
Shidong Shi: National University of Singapore
Salma Jalal: National University of Singapore
Samuel F. H. Barnett: National University of Singapore
Pakorn Kanchanawong: National University of Singapore
Wenmao Huang: National University of Singapore
Jie Yan: National University of Singapore
Yong Ann Ben Lim: National University of Singapore
Visalatchi Thiagarajan: National University of Singapore
Alex Mogilner: New York University
Alexander D. Bershadsky: National University of Singapore

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Deviations from mirror symmetry in the development of bilateral organisms are common but the mechanisms of initial symmetry breaking are insufficiently understood. The actin cytoskeleton of individual cells self-organises in a chiral manner, but the molecular players involved remain essentially unidentified and the relationship between chirality of an individual cell and cell collectives is unclear. Here, we analysed self-organisation of the chiral actin cytoskeleton in individual cells on circular or elliptical patterns, and collective cell alignment in confined microcultures. Screening based on deep-learning analysis of actin patterns identified actin polymerisation regulators, depletion of which suppresses chirality (mDia1) or reverses chirality direction (profilin1 and CapZβ). The reversed chirality is mDia1-independent but requires the function of actin-crosslinker α−actinin1. A robust correlation between the effects of a variety of actin assembly regulators on chirality of individual cells and cell collectives is revealed. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry.

Date: 2023
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DOI: 10.1038/s41467-023-35918-1

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