Uncovering the pathophysiological mechanisms of neurodevelopmental disorders associated with ribosomopathies using Drosophila

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07796
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Chiyonobu Tomohiro 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40571659)
• Co-Investigator(Kenkyū-buntansha): 吉田 英樹 京都工芸繊維大学, 応用生物学系, 准教授 (30570600)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 神経発達症 / リボソーム / ショウジョウバエ

Outline of Final Research Achievements

Genetic defects in ribosome biogenesis result in a group of diseases called ribosomopathies. Patients with ribosomopathies manifest multiorgan phenotypes, including neurodevelopmental disorders (NDDs). A well-characterized ribosomopathy, Shwachman-Diamond syndrome (SDS), is mainly associated with loss-of-function mutations in SBDS. In the present study, we investigated the phenotypes of Drosophila melanogaster following knockdown of the Drosophila ortholog of SBDS, CG8549, to directly study the neurological consequences. The pan-neuron-specific knockdown of CG8549 results in learning impairments, locomotive disabilities, hyperactivity, mechanically induced seizures, and anatomical defects in presynaptic terminals. Screening genes that interact with CG8549 by using this model will contribute to a better understanding of the pathogenesis of NDDs induced by defects in ribosomal biogenesis.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

近年、神経発達症の病態としてリボソーム機能障害が着目されているが、神経症状に着目したリボソーム病のモデル生物はこれまでに報告がない。本研究で確立したショウジョウバエモデルは、リボソーム障害による神経発達症の新規治療探索研究に応用できると考えられ、学術的に意義の高い結果と考えている。