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.

journal_name

Stem Cell Res

journal_title

Stem cell research

authors

Tsan YC,Morell MH,O'Shea KS

doi

10.1016/j.scr.2016.07.003

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

238-247

issue

2

eissn

1873-5061

issn

1876-7753

pii

S1873-5061(16)30075-7

journal_volume

17

pub_type

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