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    題名: RARbeta isoform-specific regulation of DARPP-32 gene expression: An ectopic expression study in the developing telencephalon
    作者: 廖文霖
    Liao, Wen-Lin;Liu, Fu-Chin
    貢獻者: 神科所
    關鍵詞: dopamine;retinoic acid;RXR;striatum
    日期: 2005.01
    上傳時間: 2014-09-23 12:27:02 (UTC+8)
    摘要: Dopamine and adenosine 3`:5`-monophosphate-regulated phosphoprotein (DARPP-32) is a key molecule for dopamine neurotransmission. The molecular mechanisms underlying the regulation of DARPP-32 in the developing brain remains elusive. Previous studies have shown that retinoids are capable of inducing DARPP-32 in striatal cell culture, suggesting that retinoids are candidate molecules for controlling DARPP-32 expression. In the present study, we first studied the expression profiles of retinoid receptors and their associated co-factors in the developing rat telencephalon by RT-PCR. The results showed that among the retinoid receptors, RARbeta and RXRgamma were nearly selectively expressed in the developing striatum. By contrast, the retinoid receptors associated transcriptional co-factors, including the co-repressors of N-CoR and SMRT, and the co-activators of SRC-1 and P/CAF, were ubiquitously expressed in the developing telencephalon. In light of the previous findings that DARPP-32 was inducible by retinoids in striatal culture, but not in cortical culture, we hypothesized that the striatum-selective RARbeta and RXRgamma may mediate DARPP-32 induction by retinoids. To test this hypothesis, we used the gain-of-function approach to ectopically express RARbeta and RXRgamma in the developing cerebral cortex that lacked these two retinoid receptors. Ectopic expression of RARbeta1, but not RXRgamma1, up-regulated DARPP-32 in the cortical explant culture. Notably, DARPP-32 was up-regulated only by the RARbeta1 isoform, but not by other RARbeta isoforms. Our study suggests that RARbeta signaling may regulate DARPP-32 gene expression by an isoform-specific mechanism in developing telencephalic neurons. The molecular diversity of RARbeta isoforms may underlie parts of the complex gene regulation by retinoids during neural development.
    關聯: European Journal of Neuroscience,21(12),3262-3268
    資料類型: article
    顯示於類別:[神經科學研究所] 期刊論文

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