| Budget Amount *help |
¥16,730,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Research Abstract |
A member of the TNF receptor superfamily, TROY, is expressed in the brain of embryonic and adult mice. In the early embryonic forebrain, TROY was highly expressed in nestin-positive neuroepithelial cells and radial glial cells, but not in MAP2-positive postmitotic neurons. During the late embryonic and postnatal development, expression of TROY was observed in radial glial cells and astrocytes, whereas its expression was not detected in neuronal lineage cells. To investigate the functions of TROY in neural development, we overexpressed TROY in PC 12 cells. Upregulation of negative basic helix-loop-helix transcription factors, HES-5 and Id2 proteins, was observed in the TROY-overexpressing clones. Interestingly, the overexpression of TROY in PC 12 cells strongly inhibited NGF-induced neurite outgrowth with reduction of some markers of differentiated neurons, such as NF150 and TuJ1. These findings suggest that the signaling from TROY regulates neuronal differentiation. In the adult SVZ, s
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ome glial fibrillary acidic protein (GFAP) -positive cells (type B cells) are thought to be multipotent neural stem cells. TROY was mainly expressed in type B cells and in some of type C cells, i.e. uncommitted precursor cells and astroglial lineage cells, suggesting that TROY plays some roles in the regulation of gliogenesis in the adult CNS. In order to elucidate the roles of TROY in astrocytes, we generated transgenic (TG) mice overexpressing soluble TROY, which will bind the unknown ligands for TROY to block the function of endogenous TROY ligands and signaling from TROY. Ultrastructural observation of astrocytes in the brain of these TG mice revealed abnormal features of astrocytic end-feet surrounding capillaries. Intravenously injected microperoxidase markedly leaked into the brain of TG mice, suggesting the dysfunction of blood-brain-barrier (BBB) in these mice. These findings suggest that signals from TROY play important roles in the formation, maturation and maintenance of BBB. Less
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