Researchers at IRB Barcelona discover a mechanism responsible for the orientation of asymmetric division of neuroblasts.
In Drosophila melanogaster larvae, brain stem cells are called neuroblasts that, upon division, generate another stem cell and a glanglion mother cell (GMC) that is committed to differentiation. Later, the GMC specialises in neuron or glial cell (cells that support neurons). This cell division strategy, called asymmetric mitosis, allows stem cells to produce large amounts of tissue in a relatively long period of time.
In the fly these cell divisions occur following a predetermined pattern, in such a way that the daughter GMCs always emerge in the same fixed site of neuroblasts throughout successive generations. Jens Januschke and Cayetano González, both scientists at the Institute for Research in Biomedicine (IRB Barcelona), have discovered that microtubules and centrosomes, organelles that govern some cell division processes, participate in memorizing this orientation over successive generations. The study has been published in the first issue of March of the Journal of Cell Biology, edited by Rockefeller University Press.
The fact that one centrosome is permanently positioned in the neuroblast opposing the side of the meuroblast where daughter cells bud off, led González’s group to focus on this organelle and its possible role in the transmission of polarity during the division of these stem cells.
The centrosome is a cellular component that serves to anchor microtubules, which, like motorways, provide lanes along which various cell components travel. In this context, centrosomes play an essential role in the formation of the microtubule network through which chromosomes move towards opposing poles during mitosis.
To test the participation of centrosomes in neuroblast orientation, researchers treated cells with colcemide, a drug that decomposes the microtubules of the centrosome and which effect can be reversed. While untreated neuroblasts produced daughter cells in a specific region (in the most basal section), those transiently treated with this drug generated daughter cells that emerged from almost random angels with respect to the previous. Similarly, neuroblast that genetically have been modified such that they lack centrosomes, show a similar defect in polarity orientation memory. These experiments indicate that the centrosome functions in the mechanisms that serves as a polarity orientation memory over many cell divisions. The results of this study also reveal that the establishment of polarity does not depend on the external environment but is established by the cells themselves in an autonomous manner, independently of the polarity of neighbouring cells. Despite being highly controlled, the reason for the orientation memory remains unknown.
The interphase microtubule aster is a determinant of asymmetric division orientation in Drosophila neuroblasts
Januschke J.; Gonzalez C.
J Cell Biol., 2010. doi: 10.1083/jcb.200905024