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2021 Fiscal Year Final Research Report

A role of Pcdh10 in synapse elimination of the developing mouse cerebellum

Research Project

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Project/Area Number 19K16250
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionThe University of Tokyo

Principal Investigator

Watanabe Takaki  東京大学, 大学院医学系研究科(医学部), 助教 (90749798)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywords小脳 / プルキンエ細胞 / シナプス刈り込み / プロトカドヘリン / 自閉スペクトラム症
Outline of Final Research Achievements

This study elucidated the role of the autism spectrum disorder (ASD) -related gene Pcdh10 in the cerebellum. I generated Purkinje cell-specific Pcdh10 knockout mice (Pcdh10-cKO) and investigated electrophysiologically and morphologically for synapse elimination of climbing fibers. I found that PCDH10 of Purkinje cells, which is localized in climbing fiber synapses, has a function of maintaining the synapses against synapse elimination during development, resulting in a delay of climbing fiber elimination in Pcdh10-positive Purkinje cells. Behavioral analysis of Pcdh10-cKO mice in adults suggested that if the normal delay in synapse elimination of climbing fibers by Pcdh10 disappears, repetitive / inflexible behaviors and sociability, which are related to ASD-like behaviors, were enhanced in Pcdh10-cKO mice.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

今回の成果は、Pcdh10発現細胞で登上線維のシナプス刈り込みが遅れて進むこと、Pcdh10がその遅れを作り出すこと、Pcdh10による小脳の発達制御が正常な脳機能に必要であることを明らかにした。また、Pcdh10のプルキンエ細胞での役割を解明しただけでなく、小脳発達が一過的に異常になったマウスが、成体になるとASD様行動異常を引き起こすという現象の発見でもあるという学術的意義がある。発達障害のひとつであるASDを発症しうる仕組みのひとつとして、小脳の発達異常を起因とする、または含んでいる場合がある可能性を示唆しており、この理解によって治療法への開発につながるという社会的意義が考えられる。

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Published: 2023-01-30  

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