Molecular mechanisms underlying neuronal migration during neocortical development

2016 Fiscal Year Final Research Report

• Project/Area Number: 25440114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Keio University
• Principal Investigator: Hirota Yuki 慶應義塾大学, 医学部(信濃町), 講師 (00453548)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 大脳皮質 / 層構造 / ニューロン移動 / リーリンシグナル

Outline of Final Research Achievements

The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, ApoER2 and VLDLR and exerts essential roles in the formation of the mammalian layered neocortex. Here, we we found that the neurons ectopically invaded the MZ and that neuronal migration was disrupted in the intermediate zone in the Apoer2 KO mice. Expression of ApoER2 partially but significantly rescued Apoer2 KO phenotype, suggesting that ApoER2 control migratory behavior of neurons by both cell-autonomous and non-cell-autonomous manners. As for cell-autonomous functions, we found that Rap1/integrin α5 and Akt restored the failure of termination of migration beneath the MZ and neuronal migration in the IZ of Apoer2 KO mice. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing cerebral cortex.

Free Research Field

神経発生生物学