Drosophila neurogenesis

Drosophila neural stem cells (called neuroblasts) divide asymmetrically to generate neurons while maintaining their undifferentiated state, and thus they can be used as a model system to study stem cell self-renewal versus differentiation.

Work from the Doe and Prehoda labs and others has identified a suite of asymmetrically localized proteins and RNAs that promote either self-renewal or neuronal differentiation. We have completed transcriptomic and genetic screens for genes that are required for neuroblast self-renewal and neuronal differentiation. We have identified dozens of mutants with too few or too many larval neuroblasts; some of these are regulators of cortical polarity proteins, and many have yet to be characterized. Possible functions for these genes include regulation of neuroblast cell polarity, spindle orientation (misoriented spindles lead to increased neuroblast numbers), neuronal differentiation, and/or neuroblast quiescence.

Most recently, the Doe lab and others have discovered a novel population of type II neuroblasts. These differ from canonical type I neuroblasts by dividing asymmetrically to produce transit-amplifying cells called intermediate neural progenitors (INPs). INPs may be a genetically tractable model for understanding human outer subventricular zone (OSVZ) progenitors, which also generate INPs.