Regulation of neural development by acidic sugar chains via modification of morphogen activity

2016 Fiscal Year Final Research Report

• Project/Area Number: 26290027
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: IKENAKA Kazuhiro 生理学研究所, 分子細胞生理研究領域, 教授 (00144527)
• Research Collaborator: YOSHIMURA Takeshi 大阪大学, 大学院連合小児発達学研究科, 助教 (60402567) ; ISHINO Yugo ; HASHIMOTO Hirokazu ; JIANG Wen
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糖鎖 / 神経科学 / 生理学 / 脳・神経 / 発生分化

Outline of Final Research Achievements

Sulf1/2 are endosulfatases that remove sulfate from heparan sulfate. We found that Sulf2 modulates the cell fate change from motor neurons to oligodendrocyte precursor cells (MN-to-OPC) by regulating Shh signaling in the mouse ventral spinal cord in coordination with Sulf1. Sulf mRNAs colocalized with Shh mRNA and gradually expanded dorsally from E10.5 to E12.5, following strong Patched1 signals (inducec by Shh). In the spinal cord of Sulf1 or 2 knockout (KO) mice, expression patterns of Shh and Patched1 differed from that of wild type mice. Moreover, the position of the ventral domains was shifted ventrally, MN generation prolonged, and OPC generation delayed at E12.5 in KO mice. These results demonstrated that in addition to Sulf1, Sulf2 also plays an important role in the MN-to-OPC fate change by regulating Shh signaling. Strong Shh signaling is induced when Shh is released by Sulf1/2, and this strong Shh input subsequently induces the dorsal expansion of Shh and Sulf1/2 expression.

Free Research Field

神経生物学