Molecular mechanisms of Slit-Robo signaling in the formation of neural circuits

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kyushu University (2014); Okinawa Institute of Science and Technology Graduate University (2012-2013)
• Principal Investigator: KAWADA Junichi 九州大学, 先端医療イノベーションセンター, 准教授 (00312207)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Slit-Robo / 軸索ガイダンス / 脊髄感覚神経 / 正中線 / エンドサイトーシス / リサイクリング / Arf6低分子量G蛋白質

Outline of Final Research Achievements

We studied how developing axons change responses to guidance cues, such as the repellent Slit, at the right time and place. The ventral midline is an important structure for axon guidance and also regulates the formation of neural circuits. At the midline, growing axons have to choose between two alternatives: to cross the midline or not to cross it at all. Because the midline is a repulsive barrier against most axons, commissural axons require a special strategy to cross the midline. It has been thought that a midline switch in axonal response to the repellent Slit underlies midline crossing by commissural axons. In this study, we found that functionally distinct signaling pathways composed of an Arf family GTPase and its activators Arf-GEFs (guanine exchange nucleotide factors) negatively and positively regulate this switch before and after axon midline crossing, respectively. This mechanism seems to ensure that commissural axons cross the midline only once.

Free Research Field

神経発生学