In the adult mammalian brain, new neurons are continuously generated from neural stem cells (NSCs) in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. YAP, a transcriptional co-activator of the Hippo pathway, promotes cell proliferation and inhibits differentiation in embryonic neural progenitors. However, the role of YAP in postnatal NSCs remains unclear. Here, we showed that YAP was detected in NSCs of the postnatal mouse SVZ. Forced expression of Yap promoted NSC maintenance and inhibited differentiation, whereas depletion of Yap by RNA interference or conditional knockout blocked NSC maintenance and induced neuronal differentiation. Furthermore, thyroid hormone receptor interacting protein 6 (TRIP6) recruited protein phosphatase PP1A to dephosphorylate LATS1/2, therefore inducing YAP nuclear localization and activation. Moreover, TRIP6 promoted NSC maintenance, cell proliferation and inhibited differentiation through YAP. Together, our findings demonstrate a novel interaction between YAP and TRIP6, which is critical for regulating postnatal neurogenesis in the SVZ-OB pathway.
|Effective start/end date||2017/08/01 → 2018/07/31|
- adult neurogenesis
- neural stem cell
- Hippo pathway
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