During embryogenesis, the earliest cell fate decision is tightly linked to nuclear positioning. Control of nuclear positioning arises from the integration of the different phases of activity during the cell cycle and associated cytoskeletal mechanics. Yet, the mechanisms that ensure that the correct number of nuclei move to the appropriate place remain poorly understood. We discover that in the syncytial blastoderm of Drosophila embryos spindle orientation controls which nuclei migrate towards the cortex and which ones remain inside the embryo, determining the eventual fate of the nuclei and the number of cells undergoing development. Using cytoskeletal mechanics and arguments describing the behaviour of space-filling systems, we develop a minimal theory for aster-aster interactions in an aster aggregate. Combining theoretical predictions and computational methods inspired by integral geometry with mutations in cell cycle genes, we show that spindle orientation is controlled by topological aster-aster interactions and is scale independent. Our work reveals general principles that underlie interplay between cytoskeletal mechanics with geometry and topology and how that uniquely affects density homeostasis and cell fate determination.
https://indico.ijs.si/event/1700/