| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Hidekatsu Oita University, Faculty of Medicine, Professor of Dept.of Anatomy, Biology and Medicine, 医学部, 教授 (00222430)
SUMIYOSHI Hideaki Oita University, Faculty of Medicine, Research Associate of Dept.of Anatomy, Biology and Medicine, 医学部, 助手 (60343357)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Wiring an enormous number of neurons in highly precise pattern is essential for the formation of the complex architecture of vertebrate nervous system. The formation of neural network primarily depends on the ability of growth cone, a tip of the growing axon, to interpret environmental cues along the pathway to the target region. Recent discovery of extracellular signaling molecules which act as chemoattractive cue, Netrin, and chemorepulsive cue, Semaphorin, Ephrin, and Slit, and the receptors (DCC, Eph, Robo, Plexin, and Neuropilin) has lead us to understanding of basic aspects of molecular mechanism of network, although it is far from complete because of high degree of complexity of the nervous system.
In the present study, we found chemokine SDF-1 is expressed in the optic disc of retina and optic nerve sheath during axonogenesis. We also showed that retinal ganglion cells, which are the cells bodies of retinal axon, express SDF-1 receptor CXCR4, which suggest that SDF-1 could guide
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retinal axon.
To test the possible role of SDF-1 signaling in retinal axonogenesis we knocked down SDF-1 and CXCR4 function by injecting morpholino antisense DNA into fertilized eggs. In the SDF-1 morphant retinal axons are often misrouted. They pass through the retina and go out in aberrant outlet. We generated transgenic zebrafish lines that express SDF-1 under the control of heat shock promoter HSP70. When the transgenic embryo is exposed to higher temperature (37℃) the promoter is activated and SDF-1 is induced in the embryo. We transplanted somecells from transgenic embryo into wild type embryo to have ectopic moseic type expression of SDF-1 in the recipient embryo. When transplanted cells are in the retina that is close to the retinal path, retional axons are misrouted toward the transplanted cells. These results suggest that SDF-1 attract retinal axon to guide.
We also showed that SDF-1 is expressed in the horizontal myoseptum that is the rout of lateral line primodia. We showed that SDF-1 guide lateral line primodia by using the same kind of experiments we did for retinal axons. Less
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