Characterization of TROY-expressing cells in the developing and postnatal CNS: the possible role in neuronal and glial cell development.
A member of the tumor necrosis factor receptor superfamily, TROY, is expressed in the CNS of embryonic and adult mice. In the present study, we characterized TROY-expressing cells in the embryonic and postnatal forebrain. In the early embryonic forebrain, TROY was highly expressed in nestin-positive neuroepithelial cells and radial glial cells, but not in microtubule-associated protein 2-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. In addition, TROY was exclusively expressed in Musashi-1-positive multipotent/glial progenitors in the postnatal subventricular zone. To investigate the functions of TROY in neural development, we overexpressed TROY in PC12 cells and established stably expressing cell clones. As expected, the signals from overexpressed TROY were constitutively transduced via the activation of the nuclear factor-kappaB and the c-Jun N-terminal kinase pathways in such clones. In addition, 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 PC12 cells strongly inhibited nerve growth factor-induced neurite outgrowth with reduction of some markers of differentiated neurons, such as neurofilament 150 kDa and neuron-specific beta-tubulin. These findings suggest that the signaling from TROY regulates neuronal differentiation at least in part.
Hisaoka
Tomoko
T
Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1, Kimiidera, Wakayama 641-8509, Japan.
Morikawa
Yoshihiro
Y
Komori
Tadasuke
T
Sugiyama
Takuya
T
Kitamura
Toshio
T
Senba
Emiko
E
D000818:Animals; D002454:Cell Differentiation; D002490:Central Nervous System / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D005260:Female; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016716:PC12 Cells; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C104786:Msi1h protein, mouse; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D016601:RNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor; C409471:Tnfrsf19 protein, mouse; D020932:Nerve Growth Factor