title: A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.
abstract: 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.
authors.affiliation: Department of Neurosciences, Center for Gene Expression and Drug Discovery, Beckman Research Institute of City of Hope, Duarte, California, USA.
authors.forename: Chunnian
authors.initials: C
authors.lastname: Zhao
authors.forename: GuoQiang
authors.initials: G
authors.lastname: Sun
authors.forename: Shengxiu
authors.initials: S
authors.lastname: Li
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi