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 - Funding Information:
We thank M. M. Kozlov (Tel Aviv University, Israel) and T. Hiraiwa (MBI, Singapore) for discussion, T. B. Saw (MBI, Singapore) for consulting on nematic cell orientation, M. Davidson fluorescence protein collection (The Florida State University, Tallahassee, USA), P. Roca-Cusachs, M. Pan, M. Sheetz and C. G. Koh for providing reagents, A. Wong (MBI, Singapore) for expert help in paper editing, P. Kathirvel (MBI, Singapore) and H. Chen (MBI, Singapore) for expert help in molecular work and FACS, and the SIMBA microscopy facility and nanofabrication core facility at the Mechanobiology Institute for technical help. The research is supported in part by the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE Grant No: MOE2018-T2-2-138, awarded to A.D.B; MOE2019-T2-1-099 and MOE2019-T2-02-014; awarded to P.K.), and Tier 3 (MOE Grant No: MOE2016-T3-1-002 and MOET32021-0003; awarded to A.D.B), the National Research Foundation, Prime Minister’s Office, Singapore, and the Ministry of Education under the Research Centers of Excellence program through the Mechanobiology Institute, Singapore (ref no. R-714-006-006-271), and by the Singapore Ministry of Health’s National Medical Research Council under its Open Fund - Young Individual Research Grant (Grant No: OFYIRG18may-0041; awarded to Y.H.T).
Funding Information:
We thank M. M. Kozlov (Tel Aviv University, Israel) and T. Hiraiwa (MBI, Singapore) for discussion, T. B. Saw (MBI, Singapore) for consulting on nematic cell orientation, M. Davidson fluorescence protein collection (The Florida State University, Tallahassee, USA), P. Roca-Cusachs, M. Pan, M. Sheetz and C. G. Koh for providing reagents, A. Wong (MBI, Singapore) for expert help in paper editing, P. Kathirvel (MBI, Singapore) and H. Chen (MBI, Singapore) for expert help in molecular work and FACS, and the SIMBA microscopy facility and nanofabrication core facility at the Mechanobiology Institute for technical help. The research is supported in part by the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE Grant No: MOE2018-T2-2-138, awarded to A.D.B; MOE2019-T2-1-099 and MOE2019-T2-02-014; awarded to P.K.), and Tier 3 (MOE Grant No: MOE2016-T3-1-002 and MOET32021-0003; awarded to A.D.B), the National Research Foundation, Prime Minister’s Office, Singapore, and the Ministry of Education under the Research Centers of Excellence program through the Mechanobiology Institute, Singapore (ref no. R-714-006-006-271), and by the Singapore Ministry of Health’s National Medical Research Council under its Open Fund - Young Individual Research Grant (Grant No: OFYIRG18may-0041; awarded to Y.H.T).
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 -