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- Title
Conditional Inactivation of Pen-2 in the Developing Neocortex Leads to Rapid Switch of Apical Progenitors to Basal Progenitors.
- Authors
Shanshan Cheng; Tingling Liu; Yimin Hu; Yingqian Xia; Jinxing Hou; Chaoli Huang; Xiaochuan Zou; Juan Liang; Yun Stone Shi; Yuanlin Zheng; Jun Lu; Guiquan Chen
- Abstract
The transition of apical progenitors (APs) to basal progenitors (BPs) is an important neurogenic process during cortical expansion. Presenilin enhancer 2 (Pen-2, also named as Psenen) is a key subunit of y-secretase and has been implicated in neurodevelopmental disease. However, it remains unknown how Pen-2 may regulate the maintenance of APs. To address this question, we generated a conditional KO (cKO) mouse in which Pen-2 is specifically inactivated in neural progenitor cells in the telencephalon. Both male and female embryos were used. We show that Pen-2 cKO cortices display remarkable depletion of Aps, but transient increase on BPs, compared with controls. We demonstrate that the proliferation rate of APs or BPs is not changed, but the switch of APs to BPs is dramatically accelerated in Pen-2 cKO cortices. Molecular analyses reveal decreased levels of Hesl and Hes5 but increased levels of Ngn2 and NeuroDl in Pen-2 KO cells. We report that expression of Notch 1 intracellular domain in Pen-2 cKO cortices restores the population of APs and BPs. In summary, these findings highlight a central role of the Notch signaling in Pen-2-dependent maintenance of neural stem cells in the developing neocortex.
- Subjects
NEURAL stem cells; NEOCORTEX; PROGENITOR cells
- Publication
Journal of Neuroscience, 2019, Vol 39, Issue 12, p2195
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2523-18.2019