Notch1 and Notch2 collaboratively maintain radial glial cells in mouse neurogenesis

Authors

Shun Mase, Department for Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan; Laboratory of Cell Asymmetry, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Atsunori Shitamukai, Laboratory of Cell Asymmetry, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Quan Wu, Laboratory of Cell Asymmetry, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Mitsuru Morimoto, Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Thomas Gridley, Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, 04074, United States.
Fumio Matsuzaki, Department for Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan; Laboratory of Cell Asymmetry, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. Electronic address: fumio.matsuzaki@riken.jp.

Document Type

Article

Publication Date

9-2021

Institution/Department

Center for Molecular Medicine; MaineHealth Institute for Research

Journal Title

Neuroscience research

MeSH Headings

Animals; Ependymoglial Cells; Mice; Neural Stem Cells; Neurogenesis; Receptor, Notch1 (genetics); Signal Transduction

Abstract

During mammalian corticogenesis, Notch signaling is essential to maintain neural stem cells called radial glial cells (RGCs) and the cortical architecture. Because the conventional knockout of either Notch1 or Notch2 causes a neuroepithelial loss prior to neurogenesis, their functional relationship in RGCs remain elusive. Here, we investigated the impacts of single knockout of Notch1 and Notch2 genes, and their conditional double knockout (DKO) on mouse corticogenesis. We demonstrated that Notch1 single knockout affected RGC maintenance in early to mid-neurogenesis whereas Notch2 knockout caused no apparent defect. In contrast, Notch2 plays a role in the RGC maintenance as Notch1 does at the late stage. Notch1 and Notch2 DKO resulted in the complete loss of RGCs, suggesting their cooperative function. We found that Notch activity in RGCs depends on the Notch gene dosage irrespective of Notch1 or Notch2 at late neurogenic stage, and that Notch1 and Notch2 have a similar activity, most likely due to a drastic increase in Notch2 transcription. Our results revealed that Notch1 has an essential role in establishing the RGC pool during the early stage, whereas Notch1 and Notch2 subsequently exhibit a comparable function for RGC maintenance and neurogenesis in the late neurogenic period in the mouse telencephalon.

First Page

122

Last Page

132

Recommended Citation

Mase S, Shitamukai A, Wu Q, Morimoto M, Gridley T, Matsuzaki F. Notch1 and Notch2 collaboratively maintain radial glial cells in mouse neurogenesis. Neurosci Res. 2021;170:122-132. doi:10.1016/j.neures.2020.11.007