Journal article
MiR-34a Represses Numbl in Murine Neural Progenitor Cells and Antagonizes Neuronal Differentiation
PloS one, Vol.7(6), pp.e38562-e38562
06/11/2012
DOI: 10.1371/journal.pone.0038562
PMCID: PMC3372529
PMID: 22701667
Abstract
MicroRNA (miRNA) function is required for normal animal development, in particular in differentiation pathways from stem cell and precursor populations. In neurogenesis, it is becoming increasingly appreciated that miRNAs act at many stages to ensure proper progression. In this study we examined the role of miR-34a in neural progenitor cells (NPC) derived from murine embryonic cortex. We found that over-expression of miR-34a in NPC significantly reduced the neuron yield upon in vitro induction of differentiation. MiR-34a has several predicted targets in the Notch pathway, which operates to balance progenitor self-renewal and differentiation during cortical neurogenesis. We tested several Notch pathway players for regulation by miR-34a in undifferentiated NPC, and found that mRNA and protein levels of Numbl, a negative regulator of Notch signaling, as well as two downstream pro-neural genes usually blocked by Notch signaling, NeuroD1 and Mash1, were diminished, while Notch1 and Cbf1 transcripts were enhanced by miR-34a over-expression. Using a luciferase reporter assay, we verified the Numbl 3'-UTR as a direct miR-34a target. Correspondingly, knock-down of endogenous miR-34a resulted in increased Numbl, NeuroD1 and Mash1, and reduced Notch1 transcript levels. Together these results implicate Numbl as a physiologically relevant target of miR-34a in NPC, allowing for enhanced Notch signaling and inhibition of neuronal differentiation. This work extends our understanding of miR-34a-mediated control of cell differentiation from cancer to mammalian nervous system development.
Details
- Title: Subtitle
- MiR-34a Represses Numbl in Murine Neural Progenitor Cells and Antagonizes Neuronal Differentiation
- Creators
- Sarah K. Fineberg - University of IowaPoppy Datta - University of IowaColleen S. Stein - University of IowaBeverly L. Davidson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.7(6), pp.e38562-e38562
- Publisher
- Public Library Science
- DOI
- 10.1371/journal.pone.0038562
- PMID
- 22701667
- PMCID
- PMC3372529
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Number of pages
- 10
- Grant note
- March of Dimes Roy J. Carver Trust R21DA025132 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Language
- English
- Date published
- 06/11/2012
- Academic Unit
- Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984618520902771
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