Dopachrome tautomerase (Dct) regulates neural progenitor cell proliferation
Dopachrome tautomerase (Dct) regulates neural progenitor cell proliferation
复制标题
DOI：
10.1016/j.ydbio.2006.06.006
复制
发表时间：
2006-08-15
影响因子：
2.7
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
--
作者：
Jiao, Zhongxian;Zhang, Zheng Gang;Chopp, Michael
多巴色素互变异构酶（Dct）是真黑素生物合成途径中酪氨酸酶的下游酶，在色素细胞中催化多巴色素转化为5，5-二羟基吲哚-2-羧酸（DHICA）。Dct转录受Pax 3、Sox 10和小眼症转录因子（MITF）的直接或协同调控。使用Dct-lacZ转基因小鼠，我们测量了Dct表达的空间和时间模式在体内大脑中的新皮层神经发生。在E10.5，Dct在端脑背侧的所有层中表达。在E15.5和E17.5，当皮质神经发生时，Dct的表达主要定位于神经元干细胞所在的脑室区（VZ）。BrdU掺入法测定，RNAi阻断内源性Dct可降低胚胎皮质神经前体细胞的增殖（48%，P < 0.05）。在成年脑中，Dct/Dct表达在脑室下区（SVZ）、齿状回和嗅球（OB）中减少。而在吻侧移行流（RMS）和隔区Dct表达较强。转染后48 It，Det过表达使SVZ细胞数增加260%，而Dct沉默使SVZ细胞数减少25.8%（P < 0.05）。RT-PCR分析的结果显示，在大脑中的Dct缺乏外显子7，是相同的形式的Lict中发现的神经嵴衍生的黑素细胞。我们的数据表明，Dct，以前被称为成黑素细胞标志物，调节神经祖细胞增殖。(c)2006年爱思唯尔公司All rights reserved.
DOPAchrome tautomerase (Dct) functions downstream of tyrosinase in the biosynthetic pathway of eumelanin by catalyzing the conversion of dopachrome to 5,5-dihydroxyindole-2-carboxylic acid (DHICA) in pigment cells. Dct transcription is regulated directly or synergistically by Pax3, Sox10 and microphthalmia transcription factor (MITF). Using Dct-lacZ transgenic mice, we measured the spatial and temporal pattern of Dct expression in vivo during neocortical neurogenesis in the brain. Dct was expressed in all layers of the dorsal telencephalon in E10.5. At E15.5 and E17.5 when cortical neurogenesis occurs, expression of Dct was primarily localized to the ventricular zone (VZ) where neuronal stem cells reside. Blocking endogenous Dct by RNAi decreased proliferation of embryonic cortical neural progenitor cells (by 48%, P < 0.05), as determined by BrdU incorporation. In adult brain, Dct/Dct expression decreased in the subventricular zone (SVZ), dentate gyrus and olfactory bulb (OB). However, strong expression of Dct was observed in rostral migratory stream (RMS) and septum. Overexpression of Det in SVZ cells derived from the adult mice significantly increased the number of cells by 260%, whereas silencing Dct by RNAi decreased cell numbers by 25.8% at 48 It post-nucleofection (P < 0.05). The results of RT-PCR analysis revealed that Dct in the brain lacks exon 7 and is identical to the form of Lict found in neural-crest-derived melanocytes. Our data indicate that Dct, previously known as a melanoblast marker, regulates neural progenitor cell proliferation. (c) 2006 Elsevier Inc. All rights reserved.