| Co-Investigator(Kenkyū-buntansha) |
MORIKAWA Yoshihiro Wakayama Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60230108)
KITAMURA Toshio The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (20282527)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Research Abstract |
(1)Expression and roles of TROT in the developing and adult CNS
We characterized TROY-expressing cells in the developing and adult mouse CNS, and their roles in the neural development. TROY was highly expressed in neuroepithelial cells and radial glial cells during embryonic stages. During postnatal and adult stages, TROY was expressed in the subventricular zone (SVZ), which is known to contain neural stem cells. Double-immunofluorescent staining showed that TROY-expressing cells in the postnatal SVZ were positive for Musashi-1 and negative for PSA-NCAM, indicating that TROY is expressed in uncommitted or glial precursor cells, but not in neuronal precursor cells. In addition, TROY was also expressed in the adult SVZ. In the adult SVZ, a subset of GFAP-positive cells and EGFR-positive cells are neural stem cells, which generate TuJ1- and PSA-NCAM-positive neuronal precursor cells, Triple-immunofluorescent staining for TROY,GFAP, and EGFR revealed that all TROY-expressing cells expressed
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either GFAP or EGFR. Furthermore, TROY was expressed in astroglial lineage cells in the postnatal and adult forebrain, whereas expression of TROY was not observed in TuJ1-positive neuronal precursor cells and NeuN-positive neurons throughout development, Thus, TROY was expressed in neuroepithelial-radial glia-astrocyte lineage cells, which may be in a default lineage. Overexpression of TROY in PC12 cells inhibited NGF-induced neurite outgrowth and down-regulated neuronal differentiation markers. These findings indicate that TROY may be involved in maintaining a default lineage by repressing neuronal differentiation in the developing and adult CNS.
(2)Expression of TROY in the developing olfactory system
During late embryonic and adult stages, expression of TROY mRNA and proteins was most evident in the inner part of the olfactory nerve layer (ONL-i). Double-immunofluorscence method showed that TROY-expressing cells in the ONL-i were immunoreactive for neuropeptide Y, but not for S-100 or p75 low affinity nerve growth factor receptor, indicating that TROY is expressed in OECs of the ONL-i, but not in OECs of the outer part of the ONL (ONL-o). In addition, TROY-expressing cells were gradually increased in the glomerula layer (GL) with direction from superficial to deeper layers as postnatal development proceeded from neonatal stage to adulthood. These cells stained for GFAP but not for NPY, may be astrocyte-like OECs. Moreover, some TROY-positive cells in the ONL-i of adult mice were also GFAP-positive, NPY-negative glial cells. Therefore, TROY-positive OECs may share a common lineage and alter their phenotypes by environmental influences during the development, suggesting that TROY plays some roles in the development and plasticity of the olfactory system. Less
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