Imp/IGF2BP levels modulate individual neural stem cell growth and division through <i>myc</i> mRNA stability.

Abstract

The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of <i>Drosophila</i> neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, <i>myc</i> mRNA. We show that Imp stabilises <i>myc</i> mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit <i>myc</i> mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with <i>myc</i> mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of <i>myc</i> mRNA stability fine-tunes individual neural stem cell proliferation rates.