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Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking.

Naganathan SR, Fürthauer S, Nishikawa M, Jülicher F, Grill SW - Elife (2014)

Bottom Line: Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling.Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis.Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Center, Technical University Dresden, Dresden, Germany.

ABSTRACT
Many developmental processes break left-right (LR) symmetry with a consistent handedness. LR asymmetry emerges early in development, and in many species the primary determinant of this asymmetry has been linked to the cytoskeleton. However, the nature of the underlying chirally asymmetric cytoskeletal processes has remained elusive. In this study, we combine thin-film active chiral fluid theory with experimental analysis of the C. elegans embryo to show that the actomyosin cortex generates active chiral torques to facilitate chiral symmetry breaking. Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling. Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis. Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development.

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Theoretical velocity profiles for a stripe of high myosin activity.The graph presents theoretical axial velocity vx (magenta) and chiral velocity vy (beige) profiles given a stripe of high myosin activity (blue). The gradient in myosin activity will then lead to axial flows along the gradient and directed towards the stripe as well as chiral flows orthogonal to the gradient leading to counter-rotations.DOI:http://dx.doi.org/10.7554/eLife.04165.022
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fig4s5: Theoretical velocity profiles for a stripe of high myosin activity.The graph presents theoretical axial velocity vx (magenta) and chiral velocity vy (beige) profiles given a stripe of high myosin activity (blue). The gradient in myosin activity will then lead to axial flows along the gradient and directed towards the stripe as well as chiral flows orthogonal to the gradient leading to counter-rotations.DOI:http://dx.doi.org/10.7554/eLife.04165.022

Mentions: (A) A schematic of the skew angle measurement in the AP–LR plane. Gray dashed line, initial nuclei position; black dashed line, skewed nuclei position; beige arrows, direction of cortical flow on the dorsal surface (Video 6). To the right are the chiral skew angles of ABa for non-RNAi (gray), ect-2 (RNAi) (4.5 hrs) and rga-3 (RNAi) (4.5 hrs) in the AP–LR plane. Gray circles, skew angle in individual videos; shaded areas, SEM; green horizontal lines, mean skew angle; red horizontal lines, median skew angle; yellow shaded areas, knockdown conditions with a significant difference (95% confidence with the Wilcoxon rank sum test) from the non-RNAi condition. (B) Chiral counter-rotation velocity vc for non-RNAi (gray), ect-2 (RNAi) (4.5 hrs) and rga-3 (RNAi) (4.5 hrs) quantified at the 4-cell stage during ABa cytokinesis. Note that one outlier was removed for computing mean vc for rga-3 (RNAi). The expected flow profiles from our theoretical description, given a stripe of high myosin activity (corresponding to the cleavage plane), is shown in Figure 4—figure supplement 5. (C) Overall chirality index c, for non-RNAi (gray) and for Wnt signaling genes (40 hrs RNAi) that impact the establishment of the L/R body axis. Interestingly, gsk-3 not only results in a reduced chiral counter-rotation velocity but also in an increased AP velocity (Figure 4—figure supplements 2–4). Error bars, error of the mean with 99% confidence. Yellow bars, significant difference to non-RNAi condition; brown bars, no significant difference.


Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking.

Naganathan SR, Fürthauer S, Nishikawa M, Jülicher F, Grill SW - Elife (2014)

Theoretical velocity profiles for a stripe of high myosin activity.The graph presents theoretical axial velocity vx (magenta) and chiral velocity vy (beige) profiles given a stripe of high myosin activity (blue). The gradient in myosin activity will then lead to axial flows along the gradient and directed towards the stripe as well as chiral flows orthogonal to the gradient leading to counter-rotations.DOI:http://dx.doi.org/10.7554/eLife.04165.022
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269833&req=5

fig4s5: Theoretical velocity profiles for a stripe of high myosin activity.The graph presents theoretical axial velocity vx (magenta) and chiral velocity vy (beige) profiles given a stripe of high myosin activity (blue). The gradient in myosin activity will then lead to axial flows along the gradient and directed towards the stripe as well as chiral flows orthogonal to the gradient leading to counter-rotations.DOI:http://dx.doi.org/10.7554/eLife.04165.022
Mentions: (A) A schematic of the skew angle measurement in the AP–LR plane. Gray dashed line, initial nuclei position; black dashed line, skewed nuclei position; beige arrows, direction of cortical flow on the dorsal surface (Video 6). To the right are the chiral skew angles of ABa for non-RNAi (gray), ect-2 (RNAi) (4.5 hrs) and rga-3 (RNAi) (4.5 hrs) in the AP–LR plane. Gray circles, skew angle in individual videos; shaded areas, SEM; green horizontal lines, mean skew angle; red horizontal lines, median skew angle; yellow shaded areas, knockdown conditions with a significant difference (95% confidence with the Wilcoxon rank sum test) from the non-RNAi condition. (B) Chiral counter-rotation velocity vc for non-RNAi (gray), ect-2 (RNAi) (4.5 hrs) and rga-3 (RNAi) (4.5 hrs) quantified at the 4-cell stage during ABa cytokinesis. Note that one outlier was removed for computing mean vc for rga-3 (RNAi). The expected flow profiles from our theoretical description, given a stripe of high myosin activity (corresponding to the cleavage plane), is shown in Figure 4—figure supplement 5. (C) Overall chirality index c, for non-RNAi (gray) and for Wnt signaling genes (40 hrs RNAi) that impact the establishment of the L/R body axis. Interestingly, gsk-3 not only results in a reduced chiral counter-rotation velocity but also in an increased AP velocity (Figure 4—figure supplements 2–4). Error bars, error of the mean with 99% confidence. Yellow bars, significant difference to non-RNAi condition; brown bars, no significant difference.

Bottom Line: Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling.Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis.Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Center, Technical University Dresden, Dresden, Germany.

ABSTRACT
Many developmental processes break left-right (LR) symmetry with a consistent handedness. LR asymmetry emerges early in development, and in many species the primary determinant of this asymmetry has been linked to the cytoskeleton. However, the nature of the underlying chirally asymmetric cytoskeletal processes has remained elusive. In this study, we combine thin-film active chiral fluid theory with experimental analysis of the C. elegans embryo to show that the actomyosin cortex generates active chiral torques to facilitate chiral symmetry breaking. Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling. Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis. Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development.

Show MeSH