Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system

The asymmetric segregation of cell-fate determinants and the generation of daughter cells of different sizes rely on the correct orientation and posit ion of the mitotic spindle. In the Drosophila embryo, the determinant Prosp ero is localized basally and is segregated equally to daughters of similar cell size during epidermal cell division. In contrast, during neuroblast di vision Prospero is segregated asymmetrically to the smaller daughter cell. This simple switch between symmetric and asymmetric segregation is achieved by changing the orientation of cell division: neural cells divide in a pla ne perpendicular to that of epidermoblast division. Here, by labelling mito tic spindles in living Drosophila embryos, we show that neuroblast spindles are initially formed in the same axis as epidermal cells, but rotate befor e cell division. We find that daughter cells of different sizes arise becau se the spindle itself becomes asymmetric at anaphase: apical microtubules e longate, basal microtubules shorten, and the midbody moves basally until it is positioned asymmetrically between the two spindle poles. This observati on contradicts the widely held hypothesis that the cleavage furrow is alway s placed midway between the two centrosomes.