Clarify the pathogenic mechnism of microlissencephaly

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08283
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka City University
• Principal Investigator: Jin Mingyue 大阪市立大学, 大学院医学研究科, 講師 (60740404)
• Co-Investigator(Renkei-kenkyūsha): HIROTSUNE Shinji 大阪市立大学, 大学院医学研究科, 教授 (80337526) ; MATSUMOTO Sakiko 大阪市立大学, 大学院医学研究科, 助教 (00789654) ; YAMADA Masami 福井大学, 学術研究院医学系部門, 教授 (10322851) ; YASUNAGA Takuo 九州工業大学, 大学院情報工学研究院, 教授 (60251394) ; MIYADA Takaki 名古屋大学, 医学系研究科, 教授 (70311751) ; OIWA Kazuhiro 国立研究開発法人情報通信研究機構, 未来ICT研究所, 主管研究員 (10211096) ; FURUTA Ken'ya 国立研究開発法人情報通信研究機構, 研究員 (40571831) ; TOBA Shiori 弘前医療福祉大学, 短期大学部, 教授 (40419891)
• Research Collaborator: MIYAZAWA Atsuo ; NAGAI Kakeharu ; REVERSADE Bruno ; POMP Oz
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 中枢神経形成不全 / カタニンp80 / 細胞質ダイニン / NuMA / 微小管ネットワーク

Outline of Final Research Achievements

In this project, we performed functional analyses of katanin p80, a pathogenic causing gene of microlissencephaly. This congenital neurodevelopmental disorder has the clinical features of both microcephaly and lissencephaly. To date, mutations on the genes correlated with proliferation of neural progenitors cause microcephaly, and associated with the neuronal migration induces lissencephaly. This highlight critical functions for katanin p80 during neurogenesis and neuronal migration, suggesting the existence of a common pathophysiological pathway responsible for microcephaly and lissencephaly. In this study, we demonstrated that katanin p80 regulates microtubule (MT) remodeling with NuMA (Nuclear Mitotic Apparatus protein) and cytoplasmic dynein. Our findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via microtubule organization at the centrosome/spindle pole.

Free Research Field

分子生物学