The role of the Clk2 kinase pathway in neural development and the etiology of autism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Hiroshima University
• Principal Investigator: Suzuki Atsushi 広島大学, 両生類研究センター, 准教授 (20314726)
• Co-Investigator(Kenkyū-buntansha): 竹林 公子 (鈴木) 広島大学, 両生類研究センター, 研究員 (00397910)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 自閉症 / 神経形成 / Clk2キナーゼ

Outline of Final Research Achievements

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that shows difficulties in social communications and learning. Although genes involved in the development of ASD phenotype have been identified recently, the etiology of ASD is not well understood. We showed that Clk2, an ASD-associated gene, is involved in the regulation of embryonic neural development in the model organisms Xenopus laevis and tropicalis. In this research, we found that Clk1 and Clk3, paralogs of Clk2, have a neural-inducing activity when overexpressed in the ectoderm during early Xenopus development. Moreover, functional inactivation of Clk1, Clk2, and Clk3 in embryos affects the formation of neural tissue. In conclusion, these results suggest that members of the Xenopus Clk family (Clk1, Clk2, and Clk3) are essential for vertebrate neural development and may contribute to the etiology of ASD.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

自閉症は社会性障害などを特徴とする発達障害群であり、近年、自閉症の診断を受ける子供の数は急増している。成長段階における脳の形成異常が発症原因と考えられ、自閉症に関与する遺伝子の発生過程における働きを調べることが発症幾序の理解と治療法の開発に不可欠である。本研究では、自閉症に関与することが知られているClk2と２つの類似タンパク質（Clk1とClk3）が、発生過程における神経組織の形成に重要な役割を果たすことを明らかにした。今後、Clk1, Clk2, Clk3の作用機構を調べることで、自閉症の発症幾序の理解が進むと考えられる。