The ability of stem cells to maintain a balance between self-renewal and differentiation is crucial for development and tissue homeostasis. In Drosophila neuroblasts, the tumour suppressor Numb restricts proliferation and self-renewal in differentiating daughter cells but how its activity is regulated is unclear. Here, Bingwei Lu and colleagues reveal a novel mechanism for the control of Numb activity (see p. ). They show that phosphorylation of Numb at conserved sites modulates its tumour suppressor activity and that the antagonist actions of Polo kinase and protein phosphatase 2A control Numb phosphorylation. Expression of Numb-TS4D (a phosphomimetic form of Numb) abolishes Numb activity, they report, and leads to the formation of ectopic neuroblasts. They also identify the Dronc caspase as a Numb binding partner and show that Dronc overexpression suppresses the effects of Numb-TS4D in an apoptosis-independent and possibly non-catalytic manner. By contrast, reduction of Dronc activity enhances phospho-Numb-induced ectopic neuroblast formation. Together, these results provide new insights into neural stem cell homeostasis in Drosophila.
