哺乳類大脳皮質神経細胞の7割を占める興奮性神経細胞は胎生期に主に脳室帯付近で誕生し，中間帯を通過し脳表層側へ放射状に移動する．そして、脳の最表層である辺縁帯の直下に到達すると移動を停止することにより，古い細胞を新しい細胞が追い越して配置が入れ替わる．これらの神経細胞移動様式は哺乳類の脳表面積の拡大に寄与したと考えられており，多様なシグナル経路に厳密に制御される．形成中の中枢神経系にはECMが豊富に存在し，軸索ガイダンス，髄鞘形成，シナプス形成等を制御する．一方で、胎生期大脳皮質にも中間帯と辺縁帯にCSPG等のECMが豊富に存在するがその意義は不明である。本研究では大脳皮質形成においてCSPGが神経細胞に対して「中間帯での移動の促進」と「辺縁帯直下における移動停止」という，一見正反対のマルチモーダルな機能を発揮することを手掛かりに，形成中の大脳皮質に存在するECMがどのように多機能性を発揮して神経細胞移動を制御し、層形成に貢献しているのかを明らかにする．

Excitatory neurons, which account for 70% of mammalian cortical neurons, are born mainly in or near ventricular zone during embryonic development and migrate radially through the intermediate zone to the surface of the brain. When they reach the marginal zone, the most superficial layer of the brain, they stop migrating, allowing new neurons to pass through preceding neurons and replace them. These modes of neuronal migration are thought to have contributed to the expansion of the surface area of the mammalian brain and are strictly regulated by diverse signaling pathways. The ECM is abundant in the developing CNS and regulates axonal guidance, myelination, and synapse formation. On the other hand, the embryonic cerebral cortex also contains abundant ECMs such as CSPGs in the intermediate and marginal zones, but their significance is unknown. We found that CSPGs exhibit opposite multimodal functions during cortical formation, namely, “promotion of migration in the intermediate zone” and “termination of migration just below the marginal zone.” Base on these observations, we will investigate how ECMs in the developing cerebral cortex control neuronal migration and contribute to cortical layer formation.