TY - JOUR
T1 - Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives
AU - Tee, Yee Han
AU - Goh, Wei Jia
AU - Yong, Xianbin
AU - Ong, Hui Ting
AU - Hu, Jinrong
AU - Tay, Ignacius Yan Yun
AU - Shi, Shidong
AU - Jalal, Salma
AU - Barnett, Samuel F.H.
AU - Kanchanawong, Pakorn
AU - Huang, Wenmao
AU - Yan, Jie
AU - Lim, Yong Ann Ben
AU - Thiagarajan, Visalatchi
AU - Mogilner, Alex
AU - Bershadsky, Alexander D.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-35918-1
DO - 10.1038/s41467-023-35918-1
M3 - Article
C2 - 36774346
AN - SCOPUS:85147835713
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 776
ER -