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Roles of a newly identified TNF receptor superfamily, TROY, in the nervous system

新发现的 TNF 受体超家族 TROY 在神经系统中的作用

基本信息

批准号：
16300113
负责人：
SENBA Emiko
金额：
$ 9.6万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300113/
关键词：
central nervous system development astrocyte cytokine receptor neural stem cells radial glia olfactory ensheathing cells 受容体 TROY TNFRスーパーファミリー SVZ RMS GFAP gliogenesis

项目摘要

(1)Expression and roles of TROT in the developing and adult CNSWe 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 … More 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 systemDuring 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

(1)trot在发育中和成年小鼠中枢神经系统中的表达和作用我们研究了发育中和成年小鼠中枢神经系统中Troy表达细胞的特征，以及它们在神经发育中的作用。在胚胎期，Troy在神经上皮细胞和放射状胶质细胞中高表达。在出生后和成年阶段，Troy在脑室下区(SVZ)表达，该区域已知含有神经干细胞。双重免疫荧光染色显示，出生后SVZ中表达Troy的细胞Musashi-1阳性，PSA-NCAM阴性，表明Troy在未定位的或神经胶质前体细胞中表达，而在神经元前体细胞中不表达。此外，Troy在成体SVZ中也有表达。在成年SVZ中，部分GFAP阳性细胞和EGFR阳性细胞是神经干细胞，它们产生了tuj1和pSA-ncam阳性的神经元前体细胞。Troy、GFAP和egfr的三重免疫荧光染色显示，所有Troy表达细胞都表达…。更多的是GFAP或EGFR。此外，Troy在出生后和成年前脑的星形胶质细胞系细胞中都有表达，而在TuJ1阳性的神经元前体细胞和Neun阳性神经元中整个发育过程中都没有观察到Troy的表达，因此，Troy在神经上皮-放射状胶质-星形胶质细胞系细胞中表达，可能属于默认谱系。在PC12细胞中过表达Troy可抑制NGF诱导的神经突起生长和下调神经元分化标志物。这些结果表明，Troy可能通过抑制发育和成人中枢神经系统的神经元分化而参与维持一种默认的谱系。(2)Troy在发育中的嗅觉系统中的表达在胚胎晚期和成年期，Troy的mRNA和蛋白在嗅神经层(ONL-I)的内侧表达最为明显。免疫荧光双标记法显示，在ONL-I区表达Troy的细胞对神经肽Y呈阳性反应，而对S-100或p75低亲和力神经生长因子受体不呈阳性反应，表明Troy在ONL-I区的OECs中表达，而在ONL-o区的OECs中不表达。此外，随着出生后发育从新生儿期到成年期，肾小球层(GL)中Troy表达细胞逐渐增多，从浅层到深层。这些细胞表达GFAP，但不表达NPY，可能是星形胶质细胞样嗅鞘细胞。此外，成年小鼠ONL-I中的一些Troy阳性细胞也是GFAP阳性、NPY阴性的胶质细胞。因此，Troy阳性嗅鞘细胞可能具有共同的谱系，并在发育过程中受环境影响而改变其表型，提示Troy在嗅觉系统的发育和可塑性中发挥了一定的作用。较少

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel tumor necrosis factor receptor superfamily (TNFRSF), TROY, in the central nervous system.

中枢神经系统中的新型肿瘤坏死因子受体超家族（TNFRSF），TROY。

DOI：
发表时间：
2006
期刊：
ANNALS of the New York Academy of Science (New York Academy of Sciences)
影响因子：
0
作者：
M.Kobashi-Hashida;N.Ohguro;M.Tsujikawa;T.Furukawa;A.Furukawa;N.Hashida;K.Tsujikawa;K.Nakai;Y.Tano;佐藤茂;Hisaoka T et al.;Hisaoka T et al.;Morikawa Y et al.
通讯作者：
Morikawa Y et al.

Characterization of TROY-expressing cells in the developing and postnatal CNS : the possible role in neuronal and glial cell development.

发育中和出生后中枢神经系统中表达 TROY 的细胞的特征：在神经元和神经胶质细胞发育中的可能作用。

DOI：
发表时间：
2006
期刊：
European Journal of Neuroscience (in press)
影响因子：
0
作者：
M.Kobashi-Hashida;N.Ohguro;M.Tsujikawa;T.Furukawa;A.Furukawa;N.Hashida;K.Tsujikawa;K.Nakai;Y.Tano;佐藤茂;Hisaoka T et al.
通讯作者：
Hisaoka T et al.

Characterization of TROY-expressing cells in the developing and postnatal CNS : the possible role it neuronal and glial cell development.

发育中和出生后中枢神经系统中 TROY 表达细胞的特征：神经元和神经胶质细胞发育的可能作用。

DOI：
发表时间：
2006
期刊：
European Journal of Neuroscience (in press)
影响因子：
0
作者：
M.Kobashi-Hashida;N.Ohguro;M.Tsujikawa;T.Furukawa;A.Furukawa;N.Hashida;K.Tsujikawa;K.Nakai;Y.Tano;佐藤茂;Hisaoka T et al.;Hisaoka T et al.
通讯作者：
Hisaoka T et al.

ANNALS of the New York Academy of Sciences.

纽约科学院年鉴。