Biology subjects

Pimpale, L. G.

Publications and source records attributed to Pimpale, L. G..

3 recordsLinked to original sources

bioRxiv2026

Actomyosin active torques determine body plan handedness in C. elegans

Left-right (LR) asymmetries are a defining feature of bilaterian body plans, but the mechanisms that convert molecular chirality into a conserved body-axis handedness remain unclear. In C. elegans, LR axis specification proceeds via a chiral spindle skew that establishes a handed cell-cell contact pattern (CCP) at the 6-cell stage; an arrangement that, when reversed, leads to situs inversus nematodes [1]. Chiral acto-myosin flows that arise from active chiral torques have been previously identified as the driver of this LR asymmetric spindle skew [2]. Here, we show that high amounts of Lifeact::mKate2, widely used to visualize F-actin, reverse the handedness of active torques in the cortex. We find that this results in reversed chiral acto-myosin flows during LR symmetry breaking, leading to mirrored 6-cell embryos and situs inversus nematodes. Our findings demonstrate that reversing the handedness of active torques changes the LR handedness at the organismal level and establish active chiral torques as instructive for LR axis specification in worms.

biophysics↗

bioRxiv2023

A cytokinetic ring-driven cell rotation achieves Hertwig's rule in early development

Cells tend to divide along the direction in which they are longest, as famously stated by Oscar Hertwig in 1884 in his long axis rule1,2. The orientation of the mitotic spindle determines the cell division axis3, and Hertwigs long axis rule is usually ensured by forces stemming from microtubules4. Pulling on the spindle from the cell cortex can give rise to unstable behaviors5,6, and we here set out to understand how Hertwigs long axis rule is realized in early embryonic divisions where cortical pulling forces are prevalent. We focus on early C. elegans development, where we compressed embryos to reveal that cortical pulling forces favor an alignment of the spindle with the cells short axis. Strikingly, we find that this misalignment is corrected by an actomyosin-based mechanism that rotates the entire cell, including the mitotic spindle. We uncover that myosin-driven contractility in the cytokinetic ring generates inward forces that align it with the short axis, and thereby the spindle with the long axis. A theoretical model together with experiments using slightly compressed mouse zygotes suggest that a constricting cytokinetic ring can ensure Hertwigs long axis rule in cells that are free to rotate inside a confining structure, thereby generalizing the underlying principle.

developmental biology↗

bioRxiv2021

CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking

1Proper left-right symmetry breaking is essential for animal development and in many species the actin cytoskeleton plays an instrumental role in this process. Active torque generation in the actomyosin layer promotes left-right symmetry breaking in C. elegans embryos by driving chiral counter-rotating cortical flows. While both Formins and Myosins have been implied in left-right symmetry breaking, and both can rotate actin filaments in vitro, it remains unclear if active torques in the actomyosin cortex are generated by Formins, Myosins, or both. We combined the strength of C. elegans genetics with quantitative imaging and thin film, chiral active fluid theory to show that, while Non-Muscle Myosin II activity drives cortical actomyosin flows, it is permissive for chiral counter-rotation and dispensable for chiral symmetry breaking of cortical flows. Instead, we find that CYK-1/Formin activation in RhoA foci is instructive for chiral counter-rotation and promotes in-plane, active torque generation in the actomyosin cortex. Notably, we observe that artificially generated large active RhoA patches undergo rotations with consistent handedness in a CYK-1/Formin-dependent manner. Altogether, we conclude that, CYK-1/Formin-dependent active torque generation facilitates chiral symmetry breaking of actomyosin flows and drives organismal left-right symmetry breaking in the nematode worm. 2 SignificanceActive torque generation in the actin cytoskeleton has been implicated in driving left-right symmetry breaking of developing embryos, but which molecules generate the active torque and how active torque generation is organized subcellularly remains unclear. This study shows that cortical Formin, recruited to cortical regions where RhoA signaling is active, promotes active torque generation in the actomyosin layer. We find that active torque tends to locally rotate the cortex in a clockwise fashion, which drives the emergence of chiral counter-rotating flows with consistent handedness and facilitates left-right symmetry breaking of C. elegans embryos.

developmental biology↗