Characterization of TROY/TNFRSF19/TAJ-expressing cells in the adult mouse forebrain

Abstract

A member of the tumor necrosis factor receptor superfamily (TNFRSF), TROY/TNFRSF19/TAJ, is highly expressed in the brain of adult mice. Northern blot analysis using mRNA taken from regions of the adult CNS showed the expression of TROY in all regions examined, including the olfactory bulb, cerebral cortex, striatum, and hippocampus. In situ hybridization and immunohistochemistry revealed that TROY mRNA and protein were strongly expressed in the rostral migratory stream (RMS) and subventricular zone (SVZ) of adult mice. In the adult SVZ, some glial fibrillary acidic protein (GFAP)-positive cells (type B cells) are thought to be multipotent neural stem cells. These type B cells divide slowly and generate epidermal growth factor receptor (EGFR)-positive transit-amplifying precursor cells (type C cells) in the presence of epidermal growth factor (EGF). Type C cells give rise to neuron-specific class III β-tubulin (TuJ1)-positive neuroblasts (type A cells) that migrate to the olfactory bulb along the RMS. TROY-expressing cells were GFAP-positive, EGFR-positive, and TuJ1-negative in the adult SVZ. From these findings, TROY appears to be expressed in type B and type C cells, but not in type A cells, which was supported by immunoelectron microscopy. In addition, TROY was expressed in GFAP-positive astrocytes of the various regions, such as the cerebral cortex, striatum, and hippocampus. Thus, TROY was expressed in uncommitted precursor cells and astroglial lineage cells, suggesting that TROY plays some roles in the regulation of gliogenesis in the adult CNS.

Introduction

Members of the tumor necrosis factor receptor superfamily (TNFRSF) play important roles in the regulation of diverse biological activities, including cell proliferation, differentiation, survival, and programmed cell death (Baker and Reddy, 1998, Locksley et al., 2001). Some members of TNFRSF have been studied in neural development and in pathological processes of the central nervous system (CNS), such as inflammation, cancer, and injury (Bruce et al., 1996, Roth et al., 2001, Desplat-Jego et al., 2002, Tan et al., 2002). TROY (TNFRSF expressed on the mouse embryo), also named TNFRSF19 and TAJ (Toxicity And JNK inducer), is a member of TNFRSF, and is highly expressed in the adult brain and various epithelia of embryos, including neuroepithelia (Eby et al., 2000, Kojima et al., 2000).

Previously, we have reported that TROY mRNA is strongly expressed in neuroepithelial cells and radial glial cells in the ventricular zone (VZ) of the neuroepithelia, from which the cortex, hippocampus, and thalamus develop in the early embryonic CNS (Hisaoka et al., 2003). During late embryonic and postnatal development, the expression of TROY is observed in radial glial cells, astrocytes, and multipotent/glial progenitors in the subventricular zone (SVZ) of the lateral ventricle (LV). Throughout embryonic and postnatal periods, its expression is not detected in neuronal lineage cells (Hisaoka et al., 2006). In addition, TROY is expressed in the olfactory ensheathing cells of adult mice, which support axonal growth and innervation of olfactory receptor neurons (Hisaoka et al., 2004).

Recently, it has been reported that TROY forms a functional receptor complex with Nogo receptor to regulate axonal regeneration in the dorsal root ganglion (DRG) neurons of adult mice (Shao et al., 2005, Park et al., 2005). Although Park et al. (2005) have shown that TROY is highly expressed in most parts of the adult mouse CNS, including the cerebral cortex and cerebellum, as well as most DRG and retinal ganglion neurons, the detailed expression of TROY in the adult CNS remains unclear. In this study, we characterized TROY-expressing cells in the adult CNS.