A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination
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Open Access
- 29 March 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 16 (4), 365-371
- https://doi.org/10.1038/nsmb.1576
Abstract
MicroRNAs are involved in post-transcriptional regulation of gene expression. Data now indicate that miR-9 targets the nuclear receptor TLX and vice versa, thus proposing a regulatory circuit linked to the switch between neural progenitor proliferation and differentiation. MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9–induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.Keywords
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