| Project/Area Number |
09044305
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Neuroscience in general
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| Research Institution | Osaka University |
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Principal Investigator |
MURAKAMI Fujio Osaka Univesity, Graduate School of Engineering Science, Professor, 大学院・基礎工学研究科, 教授 (20089882)
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| Co-Investigator(Kenkyū-buntansha) |
FRANK Eric ピッツバーグ大学, 医学部, 教授
WEN.-JIE Song Osaka University, Graduate School of Engineering, Associate Professor, 大学院・工学研究科, 助教授 (90216573)
YAMAMOTO Nobuhiko Osaka University, Graduate School of Engineering Science, Associate Professor, 大学院・基礎工学研究科, 助教授 (00191429)
HAMA Kiyoshi Okazaki National research Institutes, Dean, 機構長 (90028267)
TESSIER-LAVIGNE Mark University of California at San Francisco, Howard Hughes Medical Institute, Assi, 医学部, 教授
ERIC Frank Pittsuburgh Univesity, School of Medicine, Professor
ERIC Frank ピッツバーグ大学, 医学部, 教授
MARK Tessier カリフォルニア大学, 医学部, 教授
勝丸 博信 大阪大学, 大学院・基礎工学研究科, 助手 (40183264)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | floor plate / chemoattraction / chemorepulsion / culture / netrin / axon guidance / development / rat / ニューロトロフィン |
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| Research Abstract |
The vertebrate neural tube is composed of an orthogonal array of axonal tracts extending along circumferential and longitudinal axes. The fact that the basic structures of the neural tube such as the floor plate, basal plate and alar plate extend up to the caudal diencephalon raises the possibility that there is common guidance mechanisms for circumferentially growing axons in the neural tube. This actually has turned out to be the ; ventrally migrating alar plate axons such as the efferent from the deep cerebellar nuclei neurons of the rat are guided towards the ventral midline by the floor plate, secreting an attractive chemotropic signal. Evidence has been accumulating that interactions between these circumferential axons and floor plate cells play a crucial role in guiding axons across the midline. The floor plate was also found to secrete a diffusible chemorepellent(s), which drives a variety of dorsally migratingaxons away from the floor plate.
At the molecular level, while netrin-l appears to play a global role in the guidance of ventrally directed axons, netrin-l - independent mechanisms, in addition to netrin-l - dependent mechanism, also appear to be involved in the guidance of dorsally directed axons. Chemorepellents and chemoattractants in combination with a variety of growth cone resposiveness may serve to establish complicated neuronal circuitry in the vertebrate brain.
As described above, long-range chemoattraction by intermediate targets plays a key role in this process. Growing axons, however, do not stall at the intermediate targets where the chemoattractant concentration is expected to be maximal. We found, commissural axons in the metencephalon, initially attracted by a chemoattractant released from the floor plate, were shown to lose responsiveness to the chemoattractant in crossing the floor plate in vitro. Such changes in axon responsiveness to chemoattractants may enable developing axons to continue to navigate toward their final destinations.
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