Loss of PP2A Disrupts the Retention of Radial Glial Progenitors in the Telencephalic Niche to Impair the Generation for Late-Born Neurons During Cortical Development
Loss of PP2A Disrupts the Retention of Radial Glial Progenitors in the Telencephalic Niche to Impair the Generation for Late-Born Neurons During Cortical Development
复制标题
PP2A 的缺失会破坏端脑龛中放射状胶质祖细胞的保留，从而损害皮质发育过程中晚生神经元的生成。
DOI：
10.1093/cercor/bhaa042
复制
发表时间：
2020-07-01
期刊：
影响因子：
3.7
通讯作者：
Hu, Yimin
中科院分区：
文献类型：
--
作者：
Huang, Chaoli;Liu, Tingting;Hu, Yimin
Telencephalic radial glial progenitors (RGPs) are retained in the ventricular zone (VZ), the niche for neural stem cells during cortical development. However, the underlying mechanism is not well understood. To study whether protein phosphatase 2A (PP2A) may regulate the above process, we generate Ppp2c alpha conditional knockout (cKO) mice, in which PP2A catalytic subunit alpha (PP2Ac alpha) is inactivated in neural progenitor cells in the dorsal telencephalon. We show that RGPs are ectopically distributed in cortical areas outside of the VZ in Ppp2c alpha cKO embryos. Whereas deletion of PP2Ac alpha does not affect the proliferation of RGPs, it significantly impairs the generation of late-born neurons. We find complete loss of apical adherens junctions (AJs) in the ventricular membrane in Ppp2c alpha cKO cortices. We observe abundant colocalization for N-cadherin and PP2Ac alpha in control AJs. Moreover, in vitro analysis reveals direct interactions of N-cadherin to PP2Ac alpha and to beta-catenin. Overall, this study not only uncovers a novel function of PP2Ac alpha in retaining RGPs into the VZ but also demonstrates the impact of PP2A-dependent retention of RGPs on the generation for late-born neurons.
