title: miR-410 controls adult SVZ neurogenesis by targeting neurogenic genes.
abstract: Over-expression of the early neural inducer, Noggin, in nestin positive subventricular zone (SVZ), neural stem cells (NSC) promotes proliferation and neuronal differentiation of neural progenitors and inhibits the expression of a CNS-enriched microRNA-410 (miR-410) (Morell et al., 2015). When expressed in neurospheres derived from the adult SVZ, miR-410 inhibits neuronal and oligodendrocyte differentiation, and promotes astrocyte differentiation. miR-410 also reverses the increase in neuronal differentiation and decreased astroglial differentiation caused by Noggin over-expression. Conversely, inhibition of miR-410 activity promotes neuronal and decreases astroglial differentiation of NSC. Using computer prediction algorithms and luciferase reporter assays we identified multiple neurogenic genes including Elavl4 as downstream targets of miR-410 via the canonical miRNA-3'UTR interaction. Over-expression of Elavl4 transcripts without the endogenous 3'UTR rescued the decrease in neuronal differentiation caused by miR-410 overexpression. Interestingly, we also observed that miR-410 affected neurite morphology; over-expression of miR-410 resulted in the formation of short, unbranched neurites. We conclude that miR-410 expression provides a new link between BMP signaling and the crucial lineage choice of adult neural stem cells via its ability to bind and control the expression of neurogenic gene transcripts.
authors: Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States.
authors: Yao-Chang
authors: YC
authors: Tsan
authors: Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States.
authors: Maria H
authors: MH
authors: Morell
authors: Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: oshea@umich.edu.
authors: K Sue
authors: KS
authors: O'Shea
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D000067779:ELAV-Like Protein 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D020413:3' Untranslated Regions; D000070416:Antagomirs; D002352:Carrier Proteins; D000067779:ELAV-Like Protein 4; D035683:MicroRNAs; D064231:Nestin; D000099176:Noggin Protein
keywords: Astrocyte; Embryonic stem cell; MicroRNA; Neural stem cell; Neuron; Oligodendrocyte