PT - JOURNAL ARTICLE AU - Y. H. Tee AU - W. J. Goh AU - X. Yong AU - H. T. Ong AU - J. Hu AU - I. Y. Y. Tay AU - S. Shi AU - S. Jalal AU - S. F. H. Barnett AU - P. Kanchanawong AU - W. Huang AU - J. Yan AU - V. Thiagarajan AU - A. D. Bershadsky TI - Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives AID - 10.1101/2021.04.22.440942 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.04.22.440942 4099 - http://biorxiv.org/content/early/2021/04/22/2021.04.22.440942.short 4100 - http://biorxiv.org/content/early/2021/04/22/2021.04.22.440942.full AB - Deviations from mirror symmetry in the development of bilateral organisms are highly stereotypic and genetically predetermined, but their mechanisms are not sufficiently understood. At the cellular level, self-organization of the actin cytoskeleton results in chiral actin swirling, and cells in groups confined to micropatterns demonstrate chiral cell alignment. The relationship between individual and collective cell chirality is unclear, and molecular players involved remain essentially unidentified. Here, by screening major actin-associated proteins and deep-learning-based morphometric analysis of actin patterns, we found that knockdowns of specific actin polymerization regulators, such as mDia1, ARPC2, and cofilins 1&2, abolished chiral actin swirling, while depletion of profilin 1 and CapZβ, reversed its direction in an actin crosslinker α-actinin1-dependent manner. Analysis of these and other knockdowns and pharmacological treatments revealed a robust correlation between their effects on the chirality of individual cells and confined cell groups. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry.One Sentence Summary Cell chirality determined by specific regulators of actin polymerization drives left-right asymmetry emergence in cell groupsCompeting Interest StatementThe authors have declared no competing interest.