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, Alexander D. Bershadsky

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number776
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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