Next October 4 at 11 am it will take place the seminar "Regulation of active versus quiescent neural stem cells" by Ryoichiro Kageyama from the Institute for Frontier Life and Medical Sciences (iCeMS), Kyoto University, Japan. At Ramón y Cajal room (PRBB).

Abstract

Somatic stem/progenitor cells are active in embryonic tissues but quiescent in many adult tissues. Although Notch signaling is required for maintenance of both active and quiescent stem cells, the detailed mechanisms that regulate active versus quiescent stem cell states are largely unknown. In active neural stem cells, expression of the Notch effector Hes1 oscillates by negative feedback, which drives cyclic expression of the proneural gene Ascl1. While sustained expression of Ascl1 induces neuronal differentiation, oscillatory expression of Ascl1 activates proliferation of neural stem cells, suggesting that oscillations are important for active neural stem cells. Indeed, when Hes1 oscillations are dampened, proliferation of neural stem cells is impaired, which causes microcephaly. By contrast, in quiescent neural stem cells in the adult brain, Hes1 levels are higher than those in active neural stem cells, causing Ascl1 expression to be continuously suppressed. Furthermore, induction of sustained Hes1 expression represses Ascl1, inhibits neurogenesis, and maintains quiescent neural stem cells, whereas inactivation of Hes1 and its related genes up-regulates Ascl1 expression, increases neurogenesis transiently, and causes rapid depletion of neural stem cells. Conversely, induction of Ascl1 oscillations activates neural stem cells and increases neurogenesis in the adult brain. Thus, Ascl1 oscillations, which normally depend on Hes1 oscillations, regulate the active state, while high Hes1 expression and resultant Ascl1 suppression promote quiescence in neural stem cells.