miR-410 controls adult SVZ neurogenesis by targeting neurogenic genes

• Main Authors: Yao-chang Tsan, Maria H. Morell, K. Sue O'Shea
• Format: Article
• Language: English
• Published: Elsevier 2016-09-01
• Series: Stem Cell Research
• Subjects: Astrocyte; Embryonic stem cell; MicroRNA; Neural stem cell; Neuron; Oligodendrocyte
• Online Access: http://www.sciencedirect.com/science/article/pii/S1873506116300757
• ISSN: 1873-5061; 1876-7753

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.