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Publication : Loss of PP2A Disrupts the Retention of Radial Glial Progenitors in the Telencephalic Niche to Impair the Generation for Late-Born Neurons During Cortical Developmentā€ .

First Author  Huang C Year  2020
Journal  Cereb Cortex Volume  30
Issue  7 Pages  4183-4196
PubMed ID  32186707 Mgi Jnum  J:294837
Mgi Id  MGI:6454438 Doi  10.1093/cercor/bhaa042
Citation  Huang C, et al. (2020) 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. Cereb Cortex 30(7):4183-4196
abstractText  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 Ppp2calpha conditional knockout (cKO) mice, in which PP2A catalytic subunit alpha (PP2Acalpha) 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 Ppp2calpha cKO embryos. Whereas deletion of PP2Acalpha 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 Ppp2calpha cKO cortices. We observe abundant colocalization for N-cadherin and PP2Acalpha in control AJs. Moreover, in vitro analysis reveals direct interactions of N-cadherin to PP2Acalpha and to beta-catenin. Overall, this study not only uncovers a novel function of PP2Acalpha in retaining RGPs into the VZ but also demonstrates the impact of PP2A-dependent retention of RGPs on the generation for late-born neurons.
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