Balancing self-renewal and differentiation by asymmetric division: Insights from brain tumor suppressors in Drosophila neural stem cells

Abstract

Balancing self-renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self-renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self-renewal control of Drosophila NBs. We summarize molecular mechanisms of asymmetric cell division and discuss how the defects in asymmetric division lead to tumor formation. Gain-of-function or loss-of-function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the asymmetric protein localization or mitotic spindle orientation of NBs. We also discuss other mechanisms of brain tumor suppression that are beyond the control of asymmetric division. Drosophila neuroblasts represent an excellent model system to study the molecular mechanisms of asymmetric divisions during stem cell self-renewal and how defects in this system lead to tumourigenesis. © 2012 WILEY Periodicals, Inc.