Analysis of neuronal tumorigenesis using mouse models

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Isogai Eriko 千葉県がんセンター(研究所), がんゲノムセンター 実験動物研究部, 上席研究員 (40300917)
• Co-Investigator(Kenkyū-buntansha): 若林 雄一 千葉県がんセンター(研究所), がんゲノムセンター 実験動物研究部, 部長 (40303119)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: マウスモデル / 神経系腫瘍 / 神経発生

Outline of Final Research Achievements

Meis1 that is involved in maintenance of stem cells and tumorigenesis, is amplified in neuronal tumors. In Meis1 knockout mice (KO), abnormal embryonic brain was observed and proliferation of radial glial cells was decreased. When Meis1 was knocked out in neural stem cells of embryonic brain, migration of neural stem cells was impaired during cortical development. Intracranial injection of neural stem cell line overexpressing Meis1 promoted brain tumor malignancy. To search genes that play important roles in the malignant brain tumor, RNA-seq was done using RNA prepared from the tumors developed after intracranial transplantation of cells. Genes that are involved in glioblastoma and neuronal differentiation were identified. These results suggest that Meis1 could play roles in developmental process of brain and brain tumor malignancy and hence the analysis may help elucidate the mechanism of brain tumor development.

Free Research Field

神経発生、神経系腫瘍を含む神経系疾患

Academic Significance and Societal Importance of the Research Achievements

幹細胞の維持と腫瘍形成に関与するMeis1は中枢および末梢神経系の発生に重要な働きをするとともに水頭症の発症に関与している。本研究ではさらにMeis1が大脳発生や脳腫瘍の発生及び悪性化に関与することが示唆された。従って、Meis1やその下流の遺伝子が関わるネットワークを明らかにすることで、発症機構が未だ不明な神経芽種、脳腫瘍や先天性水頭症など神経系腫瘍や神経疾患の解明に発展することが期待される。