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

• 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
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• 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 / 脊髄 / マウス

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.

Research Products

• [Journal Article] The BH3-only SNARE BNip1 mediates photoreceptor apoptosis in response to vesicular fusion defects (2013)
  • Author(s): Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • Journal Title: Developmental Cell Volume: 25 Issue: 4 Pages: 374-387
  • DOI: 10.1016/j.devcel.2013.04.015
  • Peer Reviewed
• [Presentation] 正中線における軸索ガイダンスを支える分子基盤 (2014)
  • Author(s): 河田純一・内海健・康東天
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-11-25
• [Presentation] Roles of Robo endocytic trafficking in acquisition of axonal responsiveness to the repellent Slit during midline crossing
  • Author(s): Yuasa-Kawada, J., Kinoshita-Kawada, M., Yanagi, S., Masai, I., Rao, Y., Wu, J.Y.
  • Organizer: 第４６回日本発生生物学会
  • Place of Presentation: 松江くにびきメッセ
• [Presentation] 神経回路形成における軸索反応性の 不可逆性スイッチを支える分子基盤
  • Author(s): 河田純一
  • Organizer: さきがけ研究２１「認識と形成」の会
  • Place of Presentation: 基礎生物学研究所
• [Presentation] A switch required for axon crossing at the midline: crucial roles of Robo receptor endocytic trafficking and the deubiquitinase USP33
  • Author(s): Yuasa-Kawada, J., Kinoshita-Kadawa, M., Yanagi, S., Masai, I., Rao, Y., Wu, J.Y.
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Upregulation of sensitivity to the repellent Slit during midline crossing bycommissural axons
  • Author(s): Kawada, J., Kinoshita-Kadawa, M., Yanagi, S., Masai, I., Rao, Y., Wu, J.Y.
  • Organizer: 第４５回日本発生生物学会・第６４回日本細胞生物学会合同大会
  • Place of Presentation: 神戸コンベンションセンター
• [Presentation] Roles of Robo endocytic trafficking in acquisition of axonal responsiveness to the repellent Slit during midline crossing
  • Author(s): Yuasa-Kawada, J., Kinoshita-Kadawa, M., Yanagi, S., Masai, I., Rao, Y., Wu, J.Y.
  • Organizer: 第４６回日本発生生物学会
  • Place of Presentation: 松江くにびきメッセ