Excitable RhoA dynamics drive pulsed contractions in the early <i>C. elegans</i> embryo

Michaux, Jonathan; Robin, François; McFadden, William M.; Munro, Edwin

doi:10.1083/jcb.201806161

Cited by 109 publications

(194 citation statements)

References 85 publications

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“…Therefore, we conclude that GCK-1/CCM-3 are novel components of negative feedback in the cytokinetic ring. These findings advance the growing body of work showing that contractile networks in cells are not only activated by positive regulation, but also contain structural "brakes" and regulatory time-delayed negative feedback important for turnover and dynamics (Bement et al, 2015;Bischof et al, 2017;Dorn et al, 2016;Goryachev et al, 2016;Khaliullin et al, 2018;Michaux et al, 2018;Nishikawa et al, 2017).…”

Section: Introductionsupporting

confidence: 69%

“…This behavior has been increasingly used to study feedback loops in the regulation of contractility. During pulsed contractility, active RhoA recruits not only the actomyosin cytoskeleton, but also negative regulators of contractility, which in turn complete a time delayed negative feedback loop (Michaux et al, 2018;Naganathan et al, 2018;Nishikawa et al, 2017;Reymann et al, 2016). GCK-1/CCM-3 are implicated in negatively regulating RhoA (Borikova et al, 2010;Louvi et al, 2014;Zheng et al, 2010) and Figure 5G), but it is unknown whether they participate in time-delayed negative feedback.…”

Section: Gck-1/ccm-3 Negatively Regulate Contractility By Promoting Nmentioning

confidence: 99%

“…To test whether GCK-1/CCM-3 regulate negative feedback during pulsed contractility, we first examined the timing of GCK-1 localization relative to contractile pulses. It has previously been shown that localization of active RhoA precedes the localization of NMY-2, Anillin and RGA-3 all of which localize concurrently (Michaux et al, 2018). We imaged cells co-expressing GFP-tagged GCK-1 and RFP-tagged NMY-2 with high temporal resolution and tracked cortical patches during polarization to determine the kinetics of GCK-1 localization relative to the accumulation of NMY-2.…”

Section: Gck-1/ccm-3 Negatively Regulate Contractility By Promoting Nmentioning

confidence: 99%

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Novel cytokinetic ring components drive negative feedback in cortical contractility

Rehain-Bell

Werner

Doshi

et al. 2019

Preprint

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Actomyosin-driven cortical contractility is a hallmark of many biological processes. While most attention has been given to the positive regulation of contractility, it is becoming increasingly appreciated that contractility is also limited by negative regulation and mechanical brakes. The cytokinetic ring is an actomyosin contractile structure whose assembly and constriction are activated by the small GTPase RhoA. Here we describe the role of two novel cytokinetic ring components GCK-1 and CCM-3 in inhibiting contractility in the cytokinetic ring. GCK-1 and CCM-3 co-localize with essential cytokinetic ring proteins such as active RhoA, the scaffold protein anillin and non-muscle myosin II (NMM-II) during anaphase. GCK-1 and CCM-3 are interdependent for their localization and require active RhoA and anillin but not NMM-II for their recruitment to the cytokinetic furrow. Partial depletion of either GCK-1 or CCM-3 leads to an increase of active RhoA, anillin and NMM-II in the cytokinetic furrow and increased rates of furrow ingression. Furthermore, GCK-1 and CCM-3 localize to actomyosin foci during pulsed contractility of the cortical cytoskeleton during zygote polarization. Depletion of GCK-1 or CCM-3 leads to an increase in both cortical contractility and baseline active RhoA levels. Together, our findings suggest that GCK-1 and CCM-3 limit contractility during zygote polarization and

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Section: Introductionsupporting

confidence: 69%

Section: Gck-1/ccm-3 Negatively Regulate Contractility By Promoting Nmentioning

confidence: 99%

Section: Gck-1/ccm-3 Negatively Regulate Contractility By Promoting Nmentioning

confidence: 99%

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Novel cytokinetic ring components drive negative feedback in cortical contractility

Rehain-Bell

Werner

Doshi

et al. 2019

Preprint

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“…Furthermore, we assume negative Hill-type F-actin feedback on ANP activation. This introduces the previously reported negative feedback of F-Actin on the activity of Rho-GTPases (Bement et al, 2015;Michaux et al, 2018;Segal et al, 2018). Notably, in our simulations we found this feedback to increase the number of parameter combinations that produce oscillatory dynamics suggesting that this feedback merely serves to provide additional robustness (Appendix Supplementary Methods).…”

Section: Fe Modelling Of F-actin Dynamics In As Cellssupporting

confidence: 80%

Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis

Atzeni

Pasakarnis

Mosca

et al. 2020

Preprint

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Tissue morphogenesis integrates cell type-specific biochemistry and architecture, cellular force generation and mechanisms coordinating forces amongst neighbouring cells and tissues.We use finite element-based modelling to explore the interconnections at these multiple biological scales in embryonic dorsal closure, where pulsed actomyosin contractility in adjacent Amnioserosa (AS) cells powers the closure of an epidermis opening. Based on our in vivo observations, the model implements F-actin nucleation periodicity that is independent of MyoII activity. Our model reveals conditions, where depleting MyoII activity nevertheless indirectly affects oscillatory F-actin behaviour, without the need for biochemical feedback. In addition, it questions the previously proposed role of Dpp-mediated regulation of the patterned actomyosin dynamics in the AS tissue, suggesting them to be emergent. Tissue-specific Dpp interference supports the model's prediction. The model further predicts that the mechanical properties of the surrounding epidermis tissue feed back on the shaping and patterning of the AS tissue. Finally, our model's parameter space reproduces mutant phenotypes and provides predictions for their underlying cause. Our modelling approach thus reveals several unappreciated mechanistic properties of tissue morphogenesis.

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“…MyoII pulses can underly a variety of morphogenetic processes, ranging from single cell polarization to tissue scale remodeling. Although recent evidence suggests that MyoII pulses can emerge spontaneously from stochastic fluctuations and local amplification 12–15 , the spatio-temporal pattern of cortical contractility must be controlled in order to produce reproducible morphogenetic outcomes. In most studied systems, this control is achieved through the conserved RhoA GTPase signaling, which activate MyoII via Rho-associated kinase (ROCK) dependent phosphorylations of its regulatory light chain (MyoII-RLC) 1, 11, 13, 15, 16 .…”

Section: Introductionmentioning

confidence: 99%

Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability

Dehapiot

Clément

Gazsó-Gerhát

et al. 2019

Preprint

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9Tissue remodeling during embryogenesis is driven by the apical contractility of the epithelial 10 cell cortex. This behavior arises notably from Rho1/Rok induced transient accumulation of non-11 muscle myosin II (MyoII pulses) pulling on actin filaments (F-Actin) of the medio-apical 12 cortex. While recent studies begin to highlight the mechanisms governing the emergence of 13 Rho1/Rok/MyoII pulsatility in different organisms, little is known about how the F-Actin 14 organization influences this process. Focusing on Drosophila ectodermal cells during germband 15 extension and amnioserosa cells during dorsal closure, we show that the medio-apical 16 actomyosin cortex consists of two entangled F-Actin subpopulations. One exhibits pulsatile 17 dynamics of actin polymerization in a Rho1 dependent manner. The other forms a persistent 18 and homogeneous network independent of Rho1. We identify the Frl/Fmnl formin as a critical 19 nucleator of the persistent network since modulating its level, in mutants or by overexpression, 20 decreases or increases the network density. Absence of this network yields sparse connectivity 21 affecting the homogeneous force transmission to the cell boundaries. This reduces the 22 propagation range of contractile forces and results in tissue scale morphogenetic defects. Our 23 work sheds new lights on how the F-Actin cortex offers multiple levels of regulation to affect 24 epithelial cells dynamics. 25The recent advances in live imaging have shown that cortical contractility can occur in a 31 pulsatile manner, by taking the form of local and transient accumulations of MyoII, known as 32 MyoII pulses. This phenomenon was first described in the C. elegans zygote and has since been 33 reported in many other species, in both embryonic and extra-embryonic tissues 3-11 . MyoII 34 pulses can underly a variety of morphogenetic processes, ranging from single cell polarization 35 to tissue scale remodeling. Although recent evidence suggests that MyoII pulses can emerge 36 spontaneously from stochastic fluctuations and local amplification 12-15 , the spatio-temporal 37 pattern of cortical contractility must be controlled in order to produce reproducible 38 morphogenetic outcomes. In most studied systems, this control is achieved through the 39 conserved RhoA GTPase signaling, which activate MyoII via Rho-associated kinase (ROCK) 40 dependent phosphorylations of its regulatory light chain (MyoII-RLC) 1,11,13,15,16 . 41 Besides MyoII regulation, another key parameter influencing cortical contractility resides in 42 actin filament network organization and dynamics. Typically, the cortex assembles as a thin 43 network of actin filaments bound to the plasma membrane. The cortical network is both highly 44 plastic and mechanically rigid and confer to the cells the ability to adapt and exert forces on 45 their surrounding environment 2,17-19 . These remarkable properties stem from the action of more 46 than a hundred actin binding proteins (ABPs) regulating the organization and the turnover of 47 the ...

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Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo

Cited by 109 publications

References 85 publications

Novel cytokinetic ring components drive negative feedback in cortical contractility

Novel cytokinetic ring components drive negative feedback in cortical contractility

Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis

Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability

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