Dual-purpose dynamics emerge from a heterogeneous cell population in Drosophila metamorphosis

Collective cell behavior is fundamental to structure multicellular organisms. There, constituting cells always have heterogeneous properties across cell types (macro-heterogeneity) and within a cell type (micro-heterogeneity). Many studies have described the existence of heterogeneity in various systems at the cellular level, whereas little has investigated its effect on the systems. Unveiling how heterogeneity plays a role in the collective behavior would build a bridge from microscopic to macroscopic biological phenomena. We use the muscle remodeling in Drosophila as a model system, in which drastic reconstruction processes involve the physical interactions of various cells. At the early pupal stages, hundreds of hemocytes vigorously migrate and decompose the larval muscles into fragments called sarcolytes. We used in vivo and in silico approaches to understand how the dynamics of the sarcolyte population are characterized by hemocytes and other cells in the environment. Our in vivo imaging showed that the sarcolyte population gradually reduced the speed while changing the spatial arrangements. We also found that the sarcolyte dynamics involve macro-heterogeneity, namely, the coexistence of fat body cells and hemocytes, as well as micro-heterogeneity within hemocytes. To computationally evaluate the effects of factors determining the speed and arrangement of the sarcolyte population, we built a mathematical model assuming simplified interactions between sarcolytes, hemocytes, and fat body cells. Our simulations showed that, firstly, the efficient spreading and stable pattern formation of sarcolytes were together achieved by a delayed emergence of fat body cells and the micro-heterogeneity in hemocyte motility. Secondly, based on the similarity of observed and simulated network-like arrangements of sarcolytes, spatial confinement was another factor that causes the stabilization of sarcolytes. This study provides a pattern formation mechanism by which macro- and micro-heterogeneous migratory cells generate a 'dual-purpose' collective behavior-quickly spreading particles throughout the field while efficiently organizing them into an orderly arrangement.