Mechanical forces generated during tissue morphogenesis regulate cell division orientation and timing.

Cell division, cell contractility, and cell shape changes all contribute to neural tube closure. Cell division is tightly regulated by biochemical factors that influence the cell cycle and cortical proteins that regulate spindle orientation. How cell division and cell/tissue shape changes are coordinated during morphogenesis is still poorly understood. During Drosophila gastrulation, domains of cell contractility and tube formation are spatially separated from domains of cell division, providing a highly tractable system for determining the coupling of these two processes. Here, we show that contractility of mesoderm cells regulates cell division orientation during Drosophila gastrulation. We find that spindle orientation in Drosophila requires a conserved pathway of Dlg and Pins (LGN), which also orients cell division in the chick neuroepithelium. We found that Pins exhibits planar cell polarized recruitment to junctions in a manner that depends on distant apical contractility. To determine whether mechanical forces also regulate cell division timing, we have disrupted adherens junctions to halt global force generation and transmission during gastrulation. In addition, we examine the timing of cell division in snail mutant where the mesoderm doesn’t undergo contractility or invaginate that degreases force generation. We found that disrupting embryo-wide force transmission or tissue folding alters the timing of cell divisions that occur alongside morphogenetic events. Thus, our data suggest that force is required to coordinate cell divisions with cell/tissue shape changes. We will examine whether cell shape changes are also required to orient cell divisions in the mouse neural tube.