Determinants of developmental timing of neocortical neural stem cells

2021 Fiscal Year Final Research Report

• Project Area: Interplay of developmental clock and extracellular environment in brain formation
• Project/Area Number: 16H06481
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: Gotoh Yukiko 東京大学, 大学院薬学系研究科(薬学部), 教授 (70252525)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: ポリコーム / 発生時間 / 幹細胞分化運命制御 / 神経幹細胞

Outline of Final Research Achievements

A fundamental question in understanding tissue development is how resident stem cells or multipotent progenitors give rise to the various cell types in appropriate numbers and at the right locations to achieve tissue organization. Neural stem/progenitor cells (NPCs) in the mammalian neocortex initially divide symmetrically to increase their pool size (expansion phase). They then divide asymmetrically and give rise to neuronal and glial cell types in a region- and developmental stage-dependent manner and with high precision (neurogenic and gliogenic phases, respectively). In this study, we aimed to identify temporal regulators (“timers”) of these fate switches of neocortical NPCs and found a factor that may drive the transition from the expansion phase to the neurogenic phase. Moreover, we found distinct suppression modes of neurogenic genes by Polycomb group (PcG) complex, which may in part explain the transition from the neurogenic phase to the gliogenic phase.

Free Research Field

総合生物　神経科学

Academic Significance and Societal Importance of the Research Achievements

脳を作る元の細胞である神経幹細胞の運命制御メカニズムを知ることは、その異常による脳発達不全を理解する基盤知識となる。また疾患や損傷によって失われた脳の細胞を補う再生医療、あるいは薬剤スクリーニングに用いる疾患モデルとして特定の種類の脳細胞を培養系で作り出すことにも貢献することが期待される。また本研究で明らかになった神経幹細胞制御因子の進化的な違いが、脳構造の進化的な差異を説明する可能性も考えられる。