Ngn1 inhibits astrogliogenesis through induction of miR-9 during neuronal fate specification
- University of California, Los Angeles, United States
- Tongji University School of Medicine, China
- Cited 23
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Abstract
It has been postulated that a proneural factor, neurogenin 1 (Ngn1), simultaneously activates the neurogenic program and inhibits the alternative astrogliogenic program when specifying the neuronal fate. While Ngn1 substantially suppresses the activation of the astrogliogenic Jak-Stat pathway, the underlying molecular mechanism was unknown. Here, by employing in vivo and in vitro approaches, we report that Ngn1 binds to the promoter of a brain-enriched microRNA, miR-9, and activates its expression during neurogenesis. Subsequently, our in vitro study showed that miR-9 directly targets mRNAs of Lifr-beta, Il6st (gp130), and Jak1 to down-regulate these critical upstream components of the Jak-Stat pathway, achieving inhibition of Stat phosphorylation and consequently, suppression of astrogliogenesis. This study revealed Ngn1 modulated non-coding RNA epigenetic regulation during cell fate specifications.
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Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and Chancellor's Animal Research Committee (ARC) protocol #2002001 of UCLA.
Reviewing Editor
- Ben Barres, Stanford School of Medicine, United States
Publication history
- Received: February 6, 2015
- Accepted: August 12, 2015
- Accepted Manuscript published: August 13, 2015 (version 1)
- Version of Record published: September 22, 2015 (version 2)
Copyright
© 2015, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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