Pathological mechanism of abnormal brain development in thanatophoric dysplasia evaluated by using human fetal brain-derived neural stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670513
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Itoh Kyoko 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80243301)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 先天異常学 / タナトフォリック骨異形成症 / 脳形成異常 / 神経幹細胞

Outline of Final Research Achievements

Thanatophoric dysplasia (TD) is a lethal form of chondrodysplastic dwarfism caused by mutations of the fibroblast growth factor receptor 3 gene (FGFR3), in which the cerebral cortex displays a temporal overgrowth and hippocampal dysplasia. In order to investigate the molecular and morphological mechanisms of abnormal brain development, we established human neural stem cells (NSCs) which stably expressed FGFR mutations such as FGFR3-K650E, and FGFR3-R248C, as previously reported in human TD. On the other hand, we constructed the three-dimensional (3D) organoids, microscopically mimicking brain (called as minibrain) from the NSCs in vitro culture system by original culture medium and culture environment. Now we are going to construct TD-minibrain model to investigate the pathological mechanisms and develop the molecular targeted therapy in the future.

Free Research Field

発生神経生物学、神経病理学