Stabilization ofDll1mRNA by Elavl1/HuR in neuroepithelial cells undergoing mitosis
Open Access
- 15 April 2011
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 22 (8), 1227-1239
- https://doi.org/10.1091/mbc.e10-10-0808
Abstract
In the vertebrate neuroepithelium, the decision to differentiate is made by neural precursors soon after mitosis, when they are apically located. This process is controlled by lateral inhibitory signals triggered by the Delta/Notch pathway. During mitosis, the capacity of neural precursors to express the neurogenic genes Dll1 and Notch1 is maximal due to mRNA stabilization, but the mechanism controlling this process remains unknown. Here we show that Elav-like (Elavl1)/HuR becomes enriched in the cytoplasm of neuroepithelial cells undergoing mitosis and that this ribonucleoprotein interacts with the 3′ untranslated region (UTR) of Dll1 mRNA. This interaction is functionally relevant because RNAi against Elavl1 reduces the stability of Dll1–3′UTR-containing transcripts in mitosis-arrested neuroepithelial cells, and Elavl1 null-mutant heterozygous mice show decreased Dll1 expression in the developing brain in vivo. We also show that RNAi against Elavl1 diminishes the capacity of brain precursors to trigger lateral inhibitory signals to their neighbors, an observation consistent with the increase in the rate of neurogenesis which can be detected in vivo in the developing retina of Elavl1 heterozygous mice. We conclude that Elavl1/HuR facilitates the exposure of vertebrate neuronal precursors to apically located Delta/Notch signals.Keywords
This publication has 45 references indexed in Scilit:
- Hook3 Interacts with PCM1 to Regulate Pericentriolar Material Assembly and the Timing of NeurogenesisNeuron, 2010
- Somatic tetraploidy in specific chick retinal ganglion cells induced by nerve growth factorProceedings of the National Academy of Sciences of the United States of America, 2009
- Myosin II is required for interkinetic nuclear migration of neural progenitorsProceedings of the National Academy of Sciences of the United States of America, 2009
- Labeled microRNA pull-down assay system: an experimental approach for high-throughput identification of microRNA-target mRNAsNucleic Acids Research, 2009
- Regulation of Neurogenesis by Interkinetic Nuclear Migration through an Apical-Basal Notch GradientCell, 2008
- Cep120 and TACCs Control Interkinetic Nuclear Migration and the Neural Progenitor PoolNeuron, 2007
- MAPK regulation of maternal and zygotic Notch transcript stability in early developmentProceedings of the National Academy of Sciences of the United States of America, 2007
- Notch signalling in vertebrate neural developmentNature Reviews Neuroscience, 2006
- Proneural genes and the specification of neural cell typesNature Reviews Neuroscience, 2002
- Pattern Formation by Lateral Inhibition with Feedback: a Mathematical Model of Delta-Notch Intercellular SignallingJournal of Theoretical Biology, 1996