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在发育中和成年中枢神经系统中的表达和作用我们对发育中和成年中枢神经系统中表达TROY的细胞进行了表征，它们在神经发育中的作用在胚胎阶段的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，已知该区域含有神经干细胞。双重免疫荧光染色显示。出生后 SVZ 中表达 TROY 的细胞 Musashi-1 呈阳性，PSA-NCAM 呈阴性，表明 TROY 在未定型或胶质前体细胞中表达，但在神经元前体细胞中不表达。此外，TROY 在成人中也有表达。在成人 SVZ 中，一部分 GFAP 阳性细胞和 EGFR 阳性细胞是神经干细胞，可产生 TuJ1 和 PSA-NCAM 阳性神经前体细胞。 TROY、GFAP 和 EGFR 的三重免疫荧光染色显示，所有表达 TROY 的细胞都表达 GFAP 或 EGFR。此外，TROY 在出生后和成人前脑的星形胶质细胞谱系细胞中表达，而 TROY 不表达。在整个发育过程中，在 TuJ1 阳性神经前体细胞和 NeuN 阳性神经元中观察到，因此，TROY 在神经上皮放射状细胞中表达PC12 细胞中 TROY 的过度表达可抑制 NGF 诱导的神经突生长并下调神经元分化标记物，这些发现表明 TROY 可能通过抑制神经元参与维持默认谱系。 (2)发育中嗅觉系统中TROY的表达胚胎晚期和成体阶段TROY mRNA和蛋白表达最明显双免疫荧光法显示 ONL-i 内表达 TROY 的细胞对神经肽 Y 具有免疫反应性，但对 S-100 或 p75 低亲和力神经生长因子受体没有免疫反应性。，表明 TROY 在 ONL-i 的 OEC 中表达，但在 ONL 外部 (ONL-o) 的 OEC 中不表达。随着出生后发育从新生儿期到成年期，肾小球层（GL）中的细胞逐渐增加，从表层到深层，这些细胞对 GFAP 染色，但对 NPY 染色，可能是星形胶质细胞样 OEC。成年小鼠 ONL-i 中的阳性细胞也是 GFAP 阳性、NPY 阴性的神经胶质细胞，因此，TROY 阳性 OEC 可能具有共同的谱系，并通过环境影响改变其表型。在发育过程中，表明TROY在嗅觉系统的发育和可塑性方面发挥了一定作用。

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）

ANNALS of the New York Academy of Sciences.

纽约科学院年鉴。

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Hisaoka T;Morikawa Y;Kitamura T;Senba E.;Morikawa Y et al.
通讯作者：
Morikawa Y et al.

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.