Differential roles of endocytic pathways in cortical development
| Project/Area Number |
26290015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Foundation for Biomedical Research and Innovation at Kobe (2015-2018)
Keio University (2014) |
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Principal Investigator |
Kawauchi Takeshi 公益財団法人神戸医療産業都市推進機構, その他部局等, 研究員(上席・主任研究員クラス) (60397544)
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| Project Period (FY) |
2014-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | エンドサイトーシス / 脳・神経 / カドヘリン / 細胞接着 / Caveolin / 細胞・組織 / 発生・分化 / 神経科学 |
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| Outline of Final Research Achievements |
During cerebral cortical development, immature neurons show multi-step mode of migration. It was reported that the neuronal migration is associated with several neurological disorders, such as lissencephaly and dyslexia. While we and others have revealed that cytoskeletal regulation plays important roles in the neuronal migration, our recent study has indicated that endocytic pathways are also important. In this study, we have analyzed the “role-allocation” of various types of endocytosis in the neuronal migration. We show here that clathrin-independent endocytosis promotes the N-cadherin internalization, which regulates the immature neurite pruning, an essential step of the multipolar-to-bipolar transition of migrating neurons. The bipolar-shaped neurons undergo the long-distance migration, which is shown to be controlled by Dynamin- and Rab5-dependent endocytic pathways. Thus, our findings show that different endocytic machineries regulate the multi-step neuronal migration.
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| Academic Significance and Societal Importance of the Research Achievements |
大脳皮質形成における多段階の神経細胞移動は、哺乳類に特徴的な６層構造の形成に必須な発生段階である。さらに近年、神経細胞は移動中に成熟することも明らかになっており、その制御機構の解明は脳形成の基礎的な理解に重要である。また、神経細胞移動は、滑脳症などの脳奇形、失読症や自閉症などの高次脳機能疾患にも関与する可能性が示唆されていることから、本研究は医学的にも重要性が高い。このような神経科学・発生生物学的な重要性に加えて、本研究は生理的な役割が疑問視されていたクラスリン非依存性エンドサイトーシスの機能を個体レベルで明らかにしており、分子細胞生物学分野にも大きく貢献したと考える。
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Report
(6 results)
Research Products
(40 results)
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[Journal Article] The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain2015
Author(s)
Shigeaki Kanatani, Takao Honda, Michihiko Aramaki, Kanehiro Hayashi, Ken-ichiro Kubo, Mami Ishida, Daisuke H. Tanaka, Takeshi Kawauchi, Katsutoshi Sekine, Sayaka Kusuzawa, Takahiko Kawasaki, Tatsumi Hirata, Hidenori Tabata, Per Uhlen and Kazunori Nakajima
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Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume: 112(36)
Issue: 36
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells.2015
Author(s)
Ito H, Shiwaku H, Yoshida C, Homma H, Luo H, Chen X, Fujita K, Musante L, Fischer U, Frints SG, Romano C, Ikeuchi Y, Shimamura T, Imoto S, Miyano S, Muramatsu SI, Kawauchi T, Hoshino M, Sudol M, Arumughan A, Wanker EE, Rich T, Schwartz C, Matsuzaki F, Bonni A, Kalscheuer VM, Okazawa H.
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Journal Title
Mol Psychiatry
Volume: 20
Issue: 4
Pages: 459-71
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A stripak component Strip serves as a platform for early endosome organization during axon elongation.2014
Author(s)
Sakuma, C., Kawauchi, T., Haraguchi, S., Shikanai, M., Yamaguchi, Y., Gelfand, V.I., Luo, L., Miura, M., and Chihara, T.
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Journal Title
Nature Comm.
Volume: 5
Issue: 1
Pages: 5180-5180
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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