Systems‐level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry

Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems‐level genetic architecture coordinating division timing, we performed a high‐content screening for genes whose depletion produced a significant reduction in the a synchrony of d ivision between s ister cells (ADS) compared to that of wild‐type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time‐lapse imaging followed by computer‐aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development. Synopsis An RNAi screen followed by quantitative analyses of cell division timing reveals dual roles of fate determinants in temporal regulation and cell fate specification and provides a resource for analyzing the genetic control of spatiotemporal coordination during metazoan development. A high‐content screen for C. elegans genes whose depletion affects asynchrony in cell division demonstrates that fate determinants are not only essential for establishing fate asymmetry, but also important in controlling division asynchrony regardless of cellular context. Perturbation of cell fate determinants involved in the regulation of division pace frequently leads to a defective migration of the same cell. The quantitative data with cellular resolution (available in the “Phenics” Database http://phenics.icts.hkbu.edu.hk/ ) constitute a resource for inferring cell‐specific gene pathways controlling spatiotemporal coordination during fate specification or tissue growth. Graphical Abstract An RNAi screen followed by quantitative analyses of cell division timing reveals dual roles