Elucidation of molecular mechanisms of acquisition of individuality and differentiation of various types of neurons in the cerebellum

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H02538
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Hoshino Mikio 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 病態生化学研究部, 部長 (70301273)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 神経発生 / 小脳 / 転写因子 / 細胞分化 / サイクリンD1 / PROX1 / ATOH1

Outline of Final Research Achievements

It was found that granule cell progenitors (GCPs) in the cerebellum progressively lose their "undifferentiated" and "proliferative" nature and eventually differentiate into granule cells. Furthermore, in this stepwise transition, cyclin D1, which was known to activate cell proliferation, was found to stabilize the ATOH1 protein via phosphorylation, thereby maintaining the undifferentiated nature of GCPs. It was also revealed that the WNT protein, which increases with brain development, and the PROX1 molecule whose expression is induced by the WNT protein, gradually decrease the amount of cyclin D1, thereby accelerating GC development.

Free Research Field

神経発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、顆粒細胞(GCs)という神経細胞の新しい発生メカニズムとその分子基盤に関して新しい知見を多く見出すことができた。これらの成果は、顆粒細胞の発生機構だけではなく、進化的な小脳皮質の拡大機構や顆粒細胞のガン化のメカニズムに関しても多くの示唆に富んでいる。また、今回注目している分子や発生メカニズムは小脳にとどまらない。大脳皮質をはじめとする各脳領域で、これらの分子や発生メカニズムは共通しているため、小脳の研究が、脳全体の共通原理の創出につながっていくことが、今後大いに期待される。