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

Middelkoop, Teije C.; Garcia-Baucells, Júlia; Quintero-Cadena, Porfirio; Pimpale, Lokesh; Yazdi, Shahrzad; Sternberg, Paul W.; Groß, Peter; Grill, Stephan W.

doi:10.1073/pnas.2021814118

Cited by 18 publications

(11 citation statements)

References 86 publications

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“…This further supports the idea that chiral movement is not purely driven by NMMII motoring, but rather results from the release of torsional stresses in the network. The same conclusion is reached in an article on the roles of CYK-1 in chiral cortical movements in C. elegans embryos ( Middelkoop et al. , 2021 ).…”

Section: Discussionsupporting

confidence: 71%

Septins and a formin have distinct functions in anaphase chiral cortical rotation in theCaenorhabditis eleganszygote

Zaatri

Perry

Maddox

2021

MBoC

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Many cells and tissues exhibit chirality that stems from the chirality of proteins and polymers. In the C. elegans zygote actomyosin contractility drives chiral rotation of the entire cortex circumferentially around the division plane during anaphase. How contractility is translated to cell-scale chirality, and what dictates handedness, are unknown. Septins are candidate contributors to cell-scale chirality because they anchor and crosslink the actomyosin cytoskeleton. We report that septins are required for anaphase cortical rotation. In contrast, the formin CYK-1, which we found to be enriched in the posterior in early anaphase, is not required for cortical rotation, but contributes to its chirality. Simultaneous loss of septin and CYK-1 function led to abnormal and often reversed cortical rotation. Our results suggest that anaphase contractility leads to chiral rotation by releasing torsional stress generated during formin-based polymerization, which is polarized along the cell anterior-posterior axis, and which accumulates due to actomyosin network connectivity. Our findings shed light on the molecular and physical bases for cellular chirality in the C. elegans zygote. We also identify conditions in which chiral rotation fails but animals are developmentally viable, opening avenues for future work on the relationship between early embryonic cellular chirality and animal body plan. [Media: see text] [Media: see text]

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Section: Discussionsupporting

confidence: 71%

Septins and a formin have distinct functions in anaphase chiral cortical rotation in theCaenorhabditis eleganszygote

Zaatri

Perry

Maddox

2021

MBoC

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“…Some of these identified actin regulators were also reported to influence actomyosin-powered cortical flow 35 in C.elegans zygote. Both in our system and in C.elegans , formins (mDia1 and CYK-1 23 respectively) seem to be important players. This role of formin family proteins might be related to their rotation at the tip of actin filaments during polymerisation due to helical organization of actin filament 36 , 37 .…”

Section: Discussionmentioning

confidence: 71%

“…In particular, non-conventional myosins 1d and 1c are needed for asymmetric hindgut and male genitalia development in Drosophila 5 , 6 , and myosin 1d is sufficient to induce chirality in other Drosophila organs 19 . We previously proposed the role of formin family proteins in the development of actin cytoskeleton chirality 11 and several recent publications established the role of diaphanous formin in dextral snail chirality 20 , 21 , Daam formin in Drosophila hindgut and genitalia chirality 22 , and Caenorhabditis elegans CYK-1 formin in chiral cortical flow of C.elegans zygote 23 . Finally, some data indicated the involvement of the actin filament crosslinking protein α−actinin1 in emergence of chirality in cultured individual cells and multi-cell spheroids 11 , 24 .…”

Section: Introductionmentioning

confidence: 99%

Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives

et al. 2023

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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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“…The nop-1, mel-11 and ima-3 RNAi clones were obtained from the Ahringer RNAi library (Source Bioscience) (Kamath and Ahringer, 2003). The mlc-4 RNAi clone was obtained from the Hyman lab (Middelkoop et al, 2021). For single RNAi interference experiments, only the RNAi clone of interest was grown on the RNAi feeding plates.…”

Section: Methodsmentioning

confidence: 99%

Axis convergence inC. elegansembryos

Bhatnagar¹,

Nestler

Groß

et al. 2023

Preprint

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Embryos develop in a surrounding that guides key aspects of their development. For example, the anteroposterior (AP) body axis is always aligned with the geometric long axis of the surrounding eggshell in fruit flies and worms. The mechanisms that ensure convergence of the AP axis with the long axis of the eggshell remain unresolved. We investigate axis convergence in early C. elegans development, where the nascent AP axis, when misaligned, actively re-aligns to converge with the long axis of the egg. Here, we identify two physical mechanisms that underlie axis convergence. First, bulk cytoplasmic flows, driven by actomyosin cortical flows, can directly reposition the AP axis. Second, active forces generated within the pseudocleavage furrow, a transient actomyosin structure similar to a contractile ring, can drive a mechanical re-orientation such that it becomes positioned perpendicular to the long axis of the egg. This in turn ensures AP axis convergence. Numerical simulations, together with experiments that either abolish the pseudocleavage furrow or change the shape of the egg, demonstrate that the pseudocleavage furrow-dependent mechanism is the key driver of axis convergence. We conclude that active force generation within the actomyosin cortical layer drives axis convergence in the early nematode.

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

Cited by 18 publications

References 86 publications

Septins and a formin have distinct functions in anaphase chiral cortical rotation in theCaenorhabditis eleganszygote

Septins and a formin have distinct functions in anaphase chiral cortical rotation in theCaenorhabditis eleganszygote

Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives

Axis convergence inC. elegansembryos

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