Cell division in large embryos is coordinated by spatial waves of Cyclin B–Cdk1 activity that spread through the cytoplasm and affect cortical contractility. However, it is still unclear how cell size and localized activation near the nucleus shape these waves, and how the cytoplasmic signal is transmitted to the cortex. Here, we develop a reaction–diffusion model of Cyclin B–Cdk1 signaling in spherical cells with localized nuclear activation. We find that cytoplasmic waves have two distinct parts: an activation front that travels as a trigger wave, and a wave back that is controlled by inhibitory gradients in the cell cycle oscillator. Because these two parts are generated by different mechanisms, they can move at different speeds or even in opposite directions. This gives rise to different wave behaviors depending on nuclear size, nuclear position, and effective cell size. We then couple the Cdk1 signal to a cortical excitable network and show how cytoplasmic waveforms can regulate Rho–actin reactivation through inhibition of the RhoGEF Ect2. In this model, cortical patterns emerge mainly as downstream responses to cytoplasmic signaling, rather than as self-organized cortical waves. Overall, our results provide a mechanistic framework linking localized nuclear activation, cytoplasmic cell cycle waves, and cortical responses in large embryonic cells. ### Competing Interest Statement The authors have declared no competing interest.
To achieve a stereotypic lineage, each embryo of Caenorhabditis elegans follows an invariant cell differentiation process arising from a combination of cell polarisation, asymmetric or symmetric divisions, combined with intercellular signalling processes. This pattern of embryonic cell differentiation is driven by regulated segregation of molecules occurring at each cell division, including polarity proteins or cell fate determinants, transcription factors, p-granules and mRNAs. These distribution patterns are coupled with a robust spatio-temporal orchestration of cortical actin dynamics, which also plays a crucial role in these processes. However, compared to other molecular contents, how the actin per se is segregated from the first asymmetric division onward remains poorly understood. This study presents a thorough quantification of the intracellular distribution from the zygote to the 4-cell stage of key actors related to actin polymerisation: two nucleators (a formin and the Arp2/3 complex), a capping protein and E-cadherin. We additionally developed a novel method to assess actin polymerisation capacities from single blastomere extracts. We found that actin-related signatures arise at these early stages and that differential mechanisms of protein segregation and homeostasis occur, depending both on the cell pair and on the protein considered. Notably, if asymmetric divisions correlated with unequal partitioning of actin-related contents in a process linked with embryonic polarity, differences were revealed between AB daughter cells upon their separation. Taken together, these actin-related asymmetric distributions are adding a layer to the complexity of cell fate acquisition mechanisms in the early embryo. ### Competing Interest Statement The authors have declared no competing interest. Agence Nationale de la Recherche, ANR-19-CE13-0005-01
To achieve a stereotypic lineage, each embryo of Caenorhabditis elegans follows an invariant cell differentiation process arising from a combination of cell polarisation, asymmetric or symmetric divisions, combined with intercellular signalling processes. This pattern of embryonic cell differentiation is driven by regulated segregation of molecules occurring at each cell division, including polarity proteins or cell fate determinants, transcription factors, p-granules and mRNAs. These distribution patterns are coupled with a robust spatio-temporal orchestration of cortical actin dynamics, which also plays a crucial role in these processes. However, compared to other molecular contents, how the actin per se is segregated from the first asymmetric division onward remains poorly understood. This study presents a thorough quantification of the intracellular distribution from the zygote to the 4-cell stage of key actors related to actin polymerisation: two nucleators (a formin and the Arp2/3 complex), a capping protein and E-cadherin. We additionally developed a novel method to assess actin polymerisation capacities from single blastomere extracts. We found that actin-related signatures arise at these early stages and that differential mechanisms of protein segregation and homeostasis occur, depending both on the cell pair and on the protein considered. Notably, if asymmetric divisions correlated with unequal partitioning of actin-related contents in a process linked with embryonic polarity, differences were revealed between AB daughter cells upon their separation. Taken together, these actin-related asymmetric distributions are adding a layer to the complexity of cell fate acquisition mechanisms in the early embryo. ### Competing Interest Statement The authors have declared no competing interest. Agence Nationale de la Recherche, ANR-19-CE13-0005-01
@dzne The @MaFu55 Lab (#DZNE) at #BonnBrain26:
#Microglial Ca-dynamics (Eyberg, A44)
NE-modulated #microglia (Antony, A45)
#Stress-driven #synapse remodeling (Crux, A46)
#Actin control of microglia (Hoffmann, A47)
#Odor coding in #SNNs (myself, A11)
Stop by our posters today 👌
Actin cytoskeleton networks exhibit specialized architectural properties for specific cellular tasks, as determined by the actin-binding proteins (ABPs) associated with each network. Proper allocation of a limiting pool of actin monomers also helps shape the assembly of different F-actin networks. The ABP capping protein (CP) modulates F-actin network architecture through regulation of actin filament length by capping filament barbed ends. Using a combination of in vitro biochemistry and quantitative live-cell imaging, we characterize CP as a major regulator of inter-network competition between filopodia and mini-comets, two F-actin networks in the one-cell C. elegans embryo (zygote). We establish that this regulation is facilitated in part by competition for binding barbed ends between CP and the F-actin elongator formin CYK-1. Together, these results reveal a role for CP in determining F-actin network architecture and dynamics, regulating the coordination between actin assembly factors to assemble and maintain different dynamic F-actin networks, and allocation of G-actin between competing cortical F-actin networks. ### Competing Interest Statement The authors have declared no competing interest.
Actin cytoskeleton networks exhibit specialized architectural properties for specific cellular tasks, as determined by the actin-binding proteins (ABPs) associated with each network. Proper allocation of a limiting pool of actin monomers also helps shape the assembly of different F-actin networks. The ABP capping protein (CP) modulates F-actin network architecture through regulation of actin filament length by capping filament barbed ends. Using a combination of in vitro biochemistry and quantitative live-cell imaging, we characterize CP as a major regulator of inter-network competition between filopodia and mini-comets, two F-actin networks in the one-cell C. elegans embryo (zygote). We establish that this regulation is facilitated in part by competition for binding barbed ends between CP and the F-actin elongator formin CYK-1. Together, these results reveal a role for CP in determining F-actin network architecture and dynamics, regulating the coordination between actin assembly factors to assemble and maintain different dynamic F-actin networks, and allocation of G-actin between competing cortical F-actin networks. ### Competing Interest Statement The authors have declared no competing interest.
Actin flow in the cortical cytoskeleton underneath the cell membrane generates mechanical stresses that shape the cell surface. We study this mechanism using an hydrodynamic model of a compressible active gel polymerising at the membrane and undergoing turnover. We determine how actin flow, density relaxation and friction of actin with the membrane generate stress on a corrugated membrane at the linear order in deformation. Analytical solutions in limiting regimes, combined with finite element methods in the general case, provide a map of normal and tangential stresses as functions of compressibility, interfacial friction and actin turnover, and determine the conditions under which actin polymerisation can render the membrane linearly unstable. The non-linear regime is also briefly discussed.
Actin flow in the cortical cytoskeleton underneath the cell membrane generates mechanical stresses that shape the cell surface. We study this mechanism using an hydrodynamic model of a compressible active gel polymerising at the membrane and undergoing turnover. We determine how actin flow, density relaxation and friction of actin with the membrane generate stress on a corrugated membrane at the linear order in deformation. Analytical solutions in limiting regimes, combined with finite element methods in the general case, provide a map of normal and tangential stresses as functions of compressibility, interfacial friction and actin turnover, and determine the conditions under which actin polymerisation can render the membrane linearly unstable. The non-linear regime is also briefly discussed.
Rxiv cytoskeleton
Rxiv mechanobio
Fabrizio Musacchio