Mechanisms underlying the evolution and development of oRG cells in higher mammals

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15898
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kanazawa University
• Principal Investigator: Matsumoto Naoyuki 金沢大学, 医学系, 協力研究員 (20774756)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 神経前駆細胞

Outline of Final Research Achievements

In this study, we analyzed the mechanisms underlying the differentiation of oRG cells, which are neural progenitors. We searched for genes that were highly expressed in oRG cells and found that sonic hedgehog (Shh) signaling was activated in oRG cells. Activation of Shh signaling in the ferret cerebral cortex increased oRG cells, and conversely suppression of Shh signaling decreased oRG cells. We also found that activation of Shh signaling increased cortical folding, and conversely, suppressing it inhibited cortical folding. Furthermore, Shh signaling was more activated in the cerebral cortex of the ferret than in that of the mouse. These results indicate that increased Shh signaling activity in the cerebral cortex during evolution led to an increase in oRG cells and cortical folding.

Free Research Field

神経発生学

Academic Significance and Societal Importance of the Research Achievements

ヒトなどの高等哺乳動物の発達した大脳皮質には、外側放射状グリア(oRG)細胞と呼ばれる高等哺乳動物に特徴的な神経前駆細胞が存在しており、oRG細胞の進化的な増加が高等哺乳動物における大脳皮質の拡大及び高次脳機能の獲得基盤につながったと考えられている。本研究では、このoRG細胞の増加と脳回形成の分子機構を明らかにし、大脳の進化のメカニズムの一端を明らかにした。本研究で得られた成果は、高等哺乳動物に特徴的なoRG細胞の分化制御機構や大脳の進化機構の解明といった神経科学への貢献のみならず、脳異常疾患の病態解明にも発展するなど社会的波及効果も大きい。