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) promotesproliferation and neuronal differentiation of neural progenitors and inhibits theexpression ofaCNS-enrichedmicroRNA-410(miR-410)(Morelletal.,2015).Whenexpressedinneurospheresderivedfrom the adultSVZ, miR-410inhibits neuronal andoligodendrocyte differentiation, and promotes astrocyte differenti ation. 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 identi f ied 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 observedthat miR-410 affect edneurite morphology;over-expressionof miR-410resultedintheformation ofshort,unbranchedneurites. 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.