A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination

• Published in: Nature structural & molecular biology Vol. 16; no. 4; pp. 365 - 371
• Main Authors: Shi, Yanhong, Li, Shengxiu, Zhao, Chunnian, Sun, GuoQiang
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.04.2009
• Subjects: Animals; Cell Differentiation; Cell Line; Cell Proliferation; Cell receptors; Feedback; Feedback, Physiological; Gene Expression Regulation, Developmental; Genetic aspects; Genetic regulation; Mice; MicroRNAs - metabolism; Molecular biology; Neurogenesis; Neurology; Physiological aspects; Receptors, Cytoplasmic and Nuclear - biosynthesis; Ribonucleic acid; RNA; Stem cells; Stem Cells - physiology; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1576

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.