Are neuronal aggregates induced by Reelin the starting point of neocortical layers?

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K06842
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Keio University
• Principal Investigator: Hayashi Kanehiro 慶應義塾大学, 医学部(信濃町), 講師 (60373354)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 大脳新皮質 / 層構造 / Reelin / N-カドヘリン

Outline of Final Research Achievements

In the developing mammalian neocortex, neurons born in or near the ventricular zone migrate to just beneath the Marginal Zone below the brain surface, and then they subsequently accumulate with each other. In this study, we aimed to elucidate the molecular mechanism of this neuronal accumulation.
We identified cellular adhesion-related molecules that function downstream of the secreted protein Reelin, and found that their translocation into lipid rafts leads to N-cadherin-dependent cellular adhesion. We also examined a Reelin point mutant found in a pachygyria patient in terms of the extracellular secretory ability, receptor binding affinity, and effects on Reelin-induced neuronal aggregate formation, and clarified the cause of the dysfunction.

Free Research Field

神経発生学

Academic Significance and Societal Importance of the Research Achievements

哺乳類大脳新皮質の6層構造は脳の高次機能を担っており、その破綻は精神疾患の要因となりうるため、6層構造形成機構の解明は重要な課題であるが、いまだ明らかにされていない。本研究では、移動直後の神経細胞の挙動に着目して、Reelinを起点として神経細胞が互いに集合する分子メカニズムの一端を解明した。またReelinは複数の精神疾患の原因遺伝子として同定されており、その発症メカニズムを明らかにすることは医学的に急務である。本研究でPachygyria患者で見つかったReelin変異の機能不全のメカニズムを明らかにでき、この結果は、病因解明や他精神疾患の原因究明に繋がる可能性がある。