Many aspects in tissue morphogenesis are attributed to the collective behavior of the participating cells. Yet, the mechanism for emergence of dynamic tissue behavior is not understood completely. Here we report the "yoyo"-like nuclear drift movement in Drosophila syncytial embryo displays typical emergent feature of collective behavior, which is associated with pseudosynchronous nuclear division cycle. We uncover the direct correlation between the degree of asynchrony of mitosis and the nuclear collective movement. Based on experimental manipulations and numerical simulations, we find the ensemble of spindle elongation, rather than a nucleus' own spindle, is the main driving force for its drift movement. The cortical F-actin acts as viscoelastic medium to dampen the movements and plays a critical role in restoring the nuclear positions after a mitosis cycle. Our study provides insights into how the interactions between cytoskeleton as individual elements leads to collective movement of the nuclear array on a macroscopic scale.
During the initial development of syncytial embryos, nuclei go through cycles of nuclear division and spatial rearrangement. The arising spatial pattern of nuclei is important for subsequent cellularization and morphing of the embryo. Although nuclei are contained within a common cytoplasm, cytoskeletal proteins are nonuniformly packaged into regions around every nucleus. In fact, cytoskeletal elements like microtubules and their associated motor proteins exert stochastic forces between nuclei, actively driving their rearrangement. Yet, it is unknown how the stochastic forces are balanced to maintain nuclear order in light of increased nuclear density upon every round of divisions. Here, we investigate the nuclear arrangements in Drosophila melanogaster over the course of several nuclear divisions starting from interphase 11. We develop a theoretical model in which we distinguish long-ranged passive forces due to the nuclei as inclusions in the elastic matrix, namely the cytoplasm, and active, stochastic forces arising from the cytoskeletal dynamics mediated by motor proteins. We perform computer simulations and quantify the observed degree of orientational and spatial order of nuclei. Solely doubling the nuclear density upon nuclear division, the model predicts a decrease in nuclear order. Comparing results to experimental recordings of tracked nuclei, we make contradictory observations, finding an increase in nuclear order upon nuclear divisions. Our analysis of model parameters resulting from this comparison suggests that overall motor protein density as well as relative active-force amplitude has to decrease by a factor of about two upon nuclear division to match experimental observations. We therefore expect a dilution of cytoskeletal motors during the rapid nuclear division to account for the increase in nuclear order during syncytial embryo development. Experimental measurements of kinesin-5 cluster lifetimes support this theoretical finding.
Motor proteins are important for transport and force generation in a variety of cellular processes and in morphogenesis. Here, we describe a general strategy for conditional motor mutants by inserting a protease cleavage site into the ‘neck’ between the head domain and the stalk of the motor protein, making the protein susceptible to proteolytic cleavage at the neck by the corresponding protease. To demonstrate the feasibility of this approach, we inserted the cleavage site of the tobacco etch virus (TEV) protease into the neck of the tetrameric motor Kinesin-5. Application of TEV protease led to a specific depletion and functional loss of Kinesin-5 in Drosophila embryos. With our approach, we revealed that Kinesin-5 stabilizes the microtubule network during interphase in syncytial embryos. The ‘molecular guillotine’ can potentially be applied to many motor proteins because Kinesins and myosins have conserved structures with accessible neck regions.This article has an associated First Person interview with the first author of the paper.
23Many aspects in tissue morphogenesis relay on the collective behavior of 24 participating cells. Despite a good understand of the underlying individual 25 processes, the mechanism for emergence of dynamic tissue behavior is 26 unclear in most cases. Here we reveal how isotropic elongation of mitotic 27 spindles drives an anisotropic collective flow of the nuclear array in syncytial 28Drosophila embryos. We found that the asynchrony of nuclear divisions, which 29is visible as a mitotic wave front sweeping over the embryo, allows elongation 30 of mitotic spindles beyond the average of inter-nuclear distances. As a 31 consequence of this overshooting, adjacent nuclei are pushed apart in early 32interphase. Strikingly, the nuclei anisotropically move several nuclear diameter 33 away from the mitotic wave front, albeit the orientation of spindles was 34 isotropic. Shortly afterwards the nuclei return to their original position in a type 35 of elastic movement. We found that spindle overshooting drove directional 36 nuclear flow and that the elastic back and forth movement was controlled by 37 cortical actin. The nuclear array did not return to its original position in mutants 38 of the formin Dia and moved three times further away without returning in 39 mutants of the Rac activator ELMO. The actin cortex effectively acts as a 40viscoelastic material with an ELMO-depending apparent viscosity and dia-and 41ELMO-dependent apparent elasticity. Our analysis provides insight into the 42 2 molecular mechanism leading to the emergence of a collective flow 43 movement. 44 45
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