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

View ORCID ProfileY. H. Tee, W. J. Goh, X. Yong, H. T. Ong, J. Hu, I. Y. Y. Tay, S. Shi, S. Jalal, S. F. H. Barnett, P. Kanchanawong, W. Huang, J. Yan, V. Thiagarajan, A. D. Bershadsky
doi: https://doi.org/10.1101/2021.04.22.440942
Y. H. Tee
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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  • For correspondence: teeyeehan@nus.edu.sg alexander.bershadsky@weizmann.ac.il
W. J. Goh
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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X. Yong
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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H. T. Ong
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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J. Hu
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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I. Y. Y. Tay
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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S. Shi
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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S. Jalal
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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S. F. H. Barnett
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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P. Kanchanawong
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
2Department of Biomedical Engineering, National University of Singapore, Singapore 117411, Singapore
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W. Huang
3Department of Physics, National University of Singapore, Singapore 117542, Singapore
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J. Yan
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
3Department of Physics, National University of Singapore, Singapore 117542, Singapore
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V. Thiagarajan
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
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A. D. Bershadsky
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
4Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
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Abstract

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 groups

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 22, 2021.
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Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives
Y. H. Tee, W. J. Goh, X. Yong, H. T. Ong, J. Hu, I. Y. Y. Tay, S. Shi, S. Jalal, S. F. H. Barnett, P. Kanchanawong, W. Huang, J. Yan, V. Thiagarajan, A. D. Bershadsky
bioRxiv 2021.04.22.440942; doi: https://doi.org/10.1101/2021.04.22.440942
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Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives
Y. H. Tee, W. J. Goh, X. Yong, H. T. Ong, J. Hu, I. Y. Y. Tay, S. Shi, S. Jalal, S. F. H. Barnett, P. Kanchanawong, W. Huang, J. Yan, V. Thiagarajan, A. D. Bershadsky
bioRxiv 2021.04.22.440942; doi: https://doi.org/10.1101/2021.04.22.440942

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