TRIP6 regulates neural stem cell maintenance through the Notch pathway in the postnatal mammalian subventricular zone

Adult neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) pathway in the mammalian brain persists throughout life. An adaptor protein, thyroid hormone receptor interacting protein 6 (TRIP6) is required for self-renewal and proliferation and inhibits neuronal differentiation in neural stem cells (NSCs) of the SVZ. Notch signaling pathway is also necessary for NSC self-renewal and inhibits their neuronal differentiation. Furthermore, we find that TRIP6 activates the Notch signaling pathway. However, the mechanism underlying this process remains to be elucidated. Here, we performed overexpression and knockdown experiments to manipulate the expression of TRIP6 and Notch intracellular domain (NICD) in NSCs. We found that TRIP6 promoted NSC self-renewal and inhibited NSC differentiation through the Notch pathway. Western blot result showed that TRIP6 increased NICD expression in NSCs. These results suggest that TRIP6 regulates NSC properties through Notch, and provide a better understanding of the molecular mechanism of TRIP6 in NSC maintenance in the adult SVZ.