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

（1）TROT在发育和成年小鼠中枢神经系统中的表达和作用我们鉴定了发育和成年小鼠中枢神经系统中表达TROY的细胞，以及它们在神经发育中的作用。TROY在胚胎期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SVZ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的细胞对Musashi-1呈阳性，对PSA-NCAM呈阴性，表明TROY在未定型或胶质前体细胞中表达，但不在神经元前体细胞中表达。此外，TROY在成年SVZ中也有表达。在成人SVZ中，GFAP阳性细胞和EGFR阳性细胞的亚群是神经干细胞，其产生TuJ 1和PSA-NCAM阳性神经元前体细胞。TROY、GFAP和EGFR的三重免疫荧光染色显示所有表达TROY的细胞表达 ...更多信息 GFAP或EGFR。此外，TROY在出生后和成年前脑的星形胶质细胞谱系细胞中表达，而在整个发育过程中，在TuJ 1阳性神经元前体细胞和NeuN阳性神经元中未观察到TROY的表达。因此，TROY在神经上皮-放射状胶质细胞-星形胶质细胞谱系细胞中表达，这可能是默认谱系。在PC 12细胞中过表达TROY抑制了NGF诱导的神经突起生长，下调了神经元分化标志物。这些发现表明，TROY可能参与维持一个默认的谱系抑制神经元分化的发展和成人中枢神经系统。（2）TROY在嗅系统发育中的表达在胚胎晚期和成体阶段，TROY mRNA和蛋白质在嗅神经层（ONL-1）的内部表达最明显。免疫荧光双标法显示，ONL-i中TROY阳性细胞表达神经肽Y，而不表达S-100和p75低亲和力神经生长因子受体，表明TROY在ONL-i的嗅鞘细胞中表达，而在ONL-o的嗅鞘细胞中不表达。此外，随着出生后发育的进行，从新生儿阶段到成年，肾小球层（GL）中的TROY表达细胞从浅层到深层逐渐增加。这些细胞GFAP染色，但不为NPY，可能是星形胶质细胞样的嗅鞘细胞。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，这表明TROY在嗅觉系统的发育和可塑性中起一定作用。少

(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