Symmetry breaking mechanisms in Drosophila neural stem cells (360G-Wellcome-100031_Z_12_A)

The control of cell division orientation impacts on the position and function of cells. Here we focus on the genetic and mechanical control that establishes the orientation of polarity and division in stem cells. Using neural stem cells, called neuroblasts, of the developing Drosophila brain, we aim to understand how stem cells remain within niche signalling range when actively proliferating. We hypothesised that the outcome of neuroblast division provides a polarity landmark for division orientation in the next cell cycle. Consistently, we found that a neuroblast daughter cell derived signal influences Par polarity module localisation when neuroblasts divide again. We now want to identify the genes behind this symmetry-breaking event. Our results suggest that midbody-organised structures link symmetry-breaking to cortical tension anisotropies and want to test if deforming the cortex using optical tweezer microscopy can bias the orientation of Par polarity. Downstream of Par complex localisation, aPKC coordinates polarity. To dissect the pleiotropic effects of aPKC, we have generated ATP analog sensitised alleles, which are homozygous viable and can be specifically inhibited. This enables us for the first time to dissect the functions of aPKC in a temporally resolved manner that establish asymmetric cell fate localisation and cell size asymmetry.