Extracellular glycans in the brain microenvironment affect neuronal polarity and migration during cortical development

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K21067
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry; Neurophysiology / General neuroscience
• Research Institution: Nagoya University
• Principal Investigator: Miyata Shinji 名古屋大学, 生命農学研究科, 特任助教 (60533792)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: コンドロイチン硫酸 / プロテオグリカン / 神経細胞移動 / 極性形成 / 大脳皮質形成

Outline of Final Research Achievements

Cortical pyramidal neurons are generated in the ventricular zone (VZ), and migrate through the intermediate zone (IZ) into the cortical plate (CP). In the IZ, a cell-sparse area filled with large amount of the extracellular matrix (ECM) molecules, immature neurons undergo rapid morphological transition from a multipolar to a bipolar shape. However, the function of ECM molecules in this process is largely unknown. We found that sulfation patterns of chondroitin sulfate proteoglycans (CSPGs) differ between the IZ and the CP. We knocked down C4ST-1, an enzyme catalyzing 4-sulfation of chondroitin sulfate, by means of in utero electroporation. C4ST-1 knock-down neurons stalled at the IZ with multipolar morphology. We identified neurocan, a central nervous system-specific CSPG, as a major carrier protein of 4-sulfated chondroitin sulfate. These results indicate that 4-sulfated neurocan produced by neurons creates a local microenvironment that promotes the multipolar to bipolar transition.

Free Research Field

糖鎖神経生物学