Mechanical Signaling in Active Tissues
(top) Frame from a Drosophila embryogenesis video with nuclei fluorescently labeled. Having just completed its 10th cycle of coordinated nuclear division, the embryo is a syncytium comprised of nuclei at its surface and a yolk sac inside. The nuclei are mechanically coupled by a surface actin network. Image courtesy of J. Dubuis. (middle) Image analysis of nuclear division cycle 11. The positions of nuclei over the cycle are depicted as black tracks. The colored circles indicate the position of the nuclei when they divide, with color corresponding to division time (orange earlier, green later). After division, the average positions of the two daughter nuclei are used for the tracks. Spatiotemporal correlations in both nuclear division times and nuclear displacements are apparent—in particular, a wave of nuclear division spreads from each pole towards the midline. (bottom) Simulation of force dipoles in an elastic medium. Each nucleus is modeled as a force dipole that becomes activated above a stress threshold. The diamonds indicate their positions and orientations, with color corresponding to division time (red earlier, blue later). Initially, we only activate the dipoles at each pole. The final configuration is depicted here.

Mitosis in the early Drosophila embryo demonstrates spatial and temporal correlations in the form of wavefronts that travel across the embryo in each cell cycle. This coordinated phenomenon requires a signaling mechanism, which others have found to be calcium-dependent. We constructed theoretical models using either pure biochemical signaling through calcium diffusion or coupled chemical and mechanical signaling in an elastic medium. In the latter models, nuclei initiate mitosis when they experience stresses propagated by neighboring nuclei that have already divided. The mechanical models quantitatively capture the wavefront speed as it varies with cell cycle number. This cannot be acheieved with the purely biochemical signaling models. Furthermore, we can analyze nuclear displacements during these mitotic wavefronts to measure the elastic parameters of the medium. Their extracted values match and independently corroborate values required by the mechanical signaling model. These findings suggest that mechanical signaling may play an important role in mediating mitotic wavefronts. Additionally, we are currently studying a similar phenomenon in fetal chick heart tubes.

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