Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain

Zhang  YQ; Chen  YT; Xie  SZWang  LLee  YFChang  SSChang  CS

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Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain

机译：Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain

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Testicular orphan nuclear receptor 4 (TR4) has been suggested to play important roles in the development and functioning of the central nervous system (CNS). We find reduced myelination in TR4 knockout (TR4(-/-)) mice, which is particularly obvious in forebrains and in early developmental stages. Further analysis reveals that CC-1-positive (CC-1+) oligodendrocytes are decreased in TR4(-/-) forebrains. The O4+ signals are also reduced in TR4(-/-) forebrains when examined at postnatal d 7. However, the number and proliferation rate of platelet-derived growth factor receptor alpha-positive (PDGF alpha R+) oligodendrocyte precursor cells (OPCs) remain unaffected in these regions, suggesting that loss of TR4 interrupts oligodendrocyte differentiation. This is further supported by the observation that CC-1+ oligodendrocytes derived from 5-bromo-2'-deoxyuridine incorporating OPCs are significantly reduced in TR4(-/-) forebrains. We also find higher Jagged1 expression levels in axon fiber-enriched regions in TR4(-/-) forebrains, suggesting a more activated Notch signaling in these regions that correlates with previous reports showing that Notch activation inhibits oligodendrocyte differentiation. Together, our results suggest that TR4 is required for proper myelination in the CNS and is particularly important for oligodendrocyte differentiation and maturation in the forebrain regions. The altered Jagged1-Notch signaling in TR4(-/-) forebrain underlies a potential mechanism that contributes to the reduced myelination in the forebrain.

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《Molecular Endocrinology》 |2007年第4期|908-920|共13页
作者
Zhang YQ; Chen YT; Xie SZWang LLee YFChang SSChang CS;
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作者单位

Univ Rochester, Med Ctr, George Whipple Lab Canc Res, Dept Pathol, Rochester, NY 14642 USA;

Univ Rochester, Med Ctr, George Whipple Lab Canc Res, Dept Urol, Rochester, NY 14642 USA;

Univ Rochester, Med Ctr, George Whipple Lab Canc Res, Dept Radiat Oncol, Rochester, NY 14642 USAUniv Rochester, Med Ctr, Ctr Canc, Rochester, NY 14642 USAChina Med Univ, Dept Neurol, Taichung 404, Taiwan;

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正文语种英语
中图分类内分泌腺疾病及代谢病;
关键词
CENTRAL-NERVOUS-SYSTEM; PROLIFERATOR-ACTIVATED RECEPTOR; OLIGODENDROCYTE PRECURSOR CELLS; THYROID-HORMONE RECEPTOR; STEROID-RECEPTOR; TRANSCRIPTION FACTOR; NUCLEAR RECEPTOR-4; GENE-EXPRESSION; RETINOIC ACID; DIFFERENTIATION;

Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain

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