Microexon splicing code for higher order brain functioning in human

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21444
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 45:Biology at organismal to population levels and anthropology, and related fields
• Research Institution: University of Toyama
• Principal Investigator: Yoshida Tomoyuki 富山大学, 学術研究部医学系, 准教授 (90372367)
• Co-Investigator(Kenkyū-buntansha): 田端 俊英 富山大学, 学術研究部工学系, 教授 (80303270)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 脳神経回路 / 高次脳機能 / マイクロエクソン / 選択的スプライシング

Outline of Final Research Achievements

The evolutionary mechanisms in which humans have acquired unique brain functions remain largely unknown. In this study, we focused on the microexons' splicing program of a synapse organizer gene, PTPRD, which governs synaptic target selection and synaptic properties. Comparisons of alternative splicing patterns of human and mouse PTPRD/Ptprd gene microexons using cultured mouse neurons and human iPS cell-derived neurons revealed that human PTPRD gene microexons were included in the transcripts less frequently. Furthermore, the KCl treatments to induce depolarization of neurons rapidly altered the alternative splicing patterns in both mouse and human neurons, however the direction of the KCl-treatment effects on the microexons' inclusion/exclusion was totally different between mouse and human neurons. These results suggest that the principle of activity-dependent neural network formation in human brain likely to be different from that in mouse.

Free Research Field

神経科学一般

Academic Significance and Societal Importance of the Research Achievements

本研究では脳神経回路構築において重要な役割を担うシナプスオーガナイザー遺伝子のマイクロエクソンの選択プログラムがマウスとヒトで異なることを明らかにした。本成果はヒトとマウスの間の脳神経回路構築の基本原理が異なることを示したものであり、ヒトの脳進化を紐解く重要な知見として学術的意義がある。