Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability.
eLife Sciences Publications, Ltd
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Samuels, T. J., Järvelin, A. I., Ish-Horowicz, D., & Davis, I. (2020). Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability.. Elife, 9 https://doi.org/10.7554/eLife.51529
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 Drosophila 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, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.
Brain, Mushroom Bodies, Animals, Drosophila melanogaster, RNA-Binding Proteins, DNA-Binding Proteins, Drosophila Proteins, Green Fluorescent Proteins, Transcription Factors, RNA, Messenger, In Situ Hybridization, Fluorescence, Signal Transduction, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Developmental, RNA Interference, Protein Binding, RNA Stability, Larva, Male, Neural Stem Cells
External DOI: https://doi.org/10.7554/eLife.51529
This record's URL: https://www.repository.cam.ac.uk/handle/1810/304131
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/