miR-30c and semaphorin 3A determine adult neurogenesis by regulating proliferation and differentiation of stem cells in the subventricular zones of mouse.

ABSTRACT

OBJECTIVES: Mechanisms that regulate proliferation of adult neural stem cells are largely unknown. Here, we have investigated the role of microR-30c (miR-30c) and its target, semaphoring 3A (sema3A), in regulating adult neurogenesis and mechanisms underlying this process. MATERIALS AND METHODS: In situ hybridization, immunofluorescence and quantitative real-time PCR were used to assess complementary expression patterns of miR-30c and sema3A in mice. Effects of miR-30c in the subventricular zone (SVZ) were examined by stereotaxic injection of up- and down-regulating lentiviruses. 5'-bromo-2'-deoxyuridine labelling was performed to investigate effects of miR-30c and sema3A on adult neurogenesis. Real-time cell assays, morphological analysis and cell cycle measurements were used to reveal the mechanisms by which miR-30c and sema3A regulate adult neurogenesis. RESULTS: Expression of miR-30c negatively correlated with that of sema3A in neurons, and levels of miR-30c and sema3A correlated positively with numbers of newborn cells in the SVZ and rostral migration stream. miR-30c and sema3A affected adult neurogenesis by regulating proliferation and differentiation, as well as cycles of stem cells in the SVZ. CONCLUSIONS: miR-30c and sema3A regulate adult neurogenesis by controlling proliferation and differentiation of stem cells in the SVZ. This finding reveals a novel regulatory mechanism of adult neurogenesis.