Dronc caspase exerts a non-apoptotic function to restrain phospho-Numb-induced ectopic neuroblast formation in Drosophila

• DOI: 10.1242/dev.058347
• Publication Date: 2011-05-10T13:23:54Z
• Authors: Yingshi Ouyang; Claudia Petritsch; Hong Wen; Lily Jan; Yuh Nung Jan; Bingwei Lu
• Keywords: 0301 basic medicine; Neurogenesis; Blotting, Western; Gene Expression; Protein Serine-Threonine Kinases; Juvenile Hormones; 03 medical and health sciences; HEK293 Cells; Neural Stem Cells; Caspases; In Situ Nick-End Labeling; Animals; Drosophila Proteins; Homeostasis; Humans; Drosophila; Phosphorylation; Protein Binding

Drosophila neuroblasts have served as a model to understand how the balance of stem cell self-renewal versus differentiation is achieved. Drosophila Numb protein regulates this process through its preferential segregation into the differentiating daughter cell. How Numb restricts the proliferation and self-renewal potentials of the recipient cell remains enigmatic. Here, we show that phosphorylation at conserved sites regulates the tumor suppressor activity of Numb. Enforced expression of a phospho-mimetic form of Numb (Numb-TS4D) or genetic manipulation that boosts phospho-Numb levels, attenuates endogenous Numb activity and causes ectopic neuroblast formation (ENF). This effect on neuroblast homeostasis occurs only in the type II neuroblast lineage. We identify Dronc caspase as a novel binding partner of Numb, and demonstrate that overexpression of Dronc suppresses the effects of Numb-TS4D in a non-apoptotic and possibly non-catalytic manner. Reduction of Dronc activity facilitates ENF induced by phospho-Numb. Our findings uncover a molecular mechanism that regulates Numb activity and suggest a novel role for Dronc caspase in regulating neural stem cell homeostasis.