Asymmetric cell division is the process through which one cell divides into two cells with different identities. It is of particular importance for stem cells, which divide asymmetrically into another stem cell (thus self-renewing themselves) and a cell destined to become a more specialised cell type, such as for example a neuron or a muscle cell. A model of choice for the study of asymmetric stem cell division are neuroblasts, neural stem cells of the fruit fly Drosophila melanogaster. Studies in neuroblasts have provided numerous insights into molecular mechanisms controlling these divisions, many of which are conserved in humans.
During the first stages of fly development, neuroblasts divide repeatedly to generate neurons. Like for many other cell types, the orientation of neuroblasts division is tightly controlled by the Par complex, a conserved group of proteins governing cell polarity (i.e. the organization of a cell in distinct domains) in animals. When a neuroblast prepares for asymmetric division, the Par complex localises to one of its pole and thus defines an axis along which the neuroblast eventually divides. Neuroblasts have the characteristic of always dividing in the same direction: at each division, the Par complex always localizes to the same pole, and the cell committed to specialisation – referred to as “daughter cell” – is always born on the opposite side. What drives the Par complex to localise to the same pole at each division has remained unclear.
The postdoc work of Nicolas Loyer in the Januschke lab, Division of Cell and Developmental Biology, recently published in Nature Communications, addresses this question. Using a combination of the powerful genetic tools of Drosophila and live imaging of neuroblasts within their native tissular environment, the study reveals that larval neuroblasts maintain their division axis by using their last-born daughter cells as a spatial cue. The interface between neuroblasts and their last-born daughter cells carries specific components, and its disruption, either by genetic techniques or by directly destroying the daughter cell using laser ablation, disrupts neuroblasts division axis maintenance. The study also sheds light on the physiological importance of division axis maintenance in neuroblasts: it ensures that neuroblasts remain properly wrapped by supporting cells, protecting neuroblasts from starvation and lack of oxygen.