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胞外核苷酸酶碱性磷酸酶和核苷三磷酸二磷酸水解酶2与小鼠胚胎期、出生后及成年神经发生区的祖细胞群体亚群相关。

The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones.

作者信息

Langer D, Ikehara Y, Takebayashi H, Hawkes R, Zimmermann H

机构信息

Institute of Cell Biology and Neuroscience, Biocenter, J.W. Goethe-University, Max-von Laue-Str. 9, 60438 Frankfurt am Main, Germany.

出版信息

Neuroscience. 2007 Dec 19;150(4):863-79. doi: 10.1016/j.neuroscience.2007.07.064. Epub 2007 Sep 12.

Abstract

Subventricular zone (SVZ)-derived adult neurospheres express two ectonucleotidases, nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) and tissue non-specific alkaline phosphatase (TNAP). Agonists of the nucleotide receptors P2Y(1) and P2Y(2) as well as adenosine augment growth factor-mediated progenitor cell proliferation. NTPDase2 converts ATP and UTP to ADP and UDP, respectively, which are all P2Y receptor agonists. TNAP hydrolyzes nucleoside triphosphates and diphosphates and produces the P1 receptor agonist adenosine. In the SVZ, NTPDase2 is specifically expressed by type B cells. In order to further scrutinize the association of key molecules of the purinergic signaling pathway with neurogenic regions, we analyzed the expression of TNAP at the lateral ventricles of the adult and developing mouse brain. In the adult brain, TNAP was expressed by type B, type A and at least subsets of type C cells of the SVZ and throughout the rostral migratory stream. Almost 100% of the proliferating, Ki-67-positive cells of the adult SVZ stained for TNAP, supporting the notion of a ubiquitous association of TNAP with SVZ progenitors. In contrast, NTPDase2-positive progenitors of the dentate gyrus were TNAP-negative. Essentially all cells of the telencephalic vesicle at embryonic day (E) 14 revealed TNAP activity, including doublecortin-positive neuroblasts. During further embryonic development, enhanced TNAP activity became restricted to cells of the ventricular and SVZ. In contrast to TNAP, NTPDase2 was first expressed in the SVZ perinatally, in association with TNAP-positive SVZ border cells. During later development, NTPDase2-positive cells disappeared from the ventricular surface and began to form sheaths around clusters of subventricular doublecortin-positive cells, apparently transforming into type B cells. Our results identify TNAP and NTPDase2 as novel markers for subsets of progenitors in the adult and developing mouse brain. They further support the notion that signaling via extracellular nucleotides and nucleosides contributes to embryonic and adult neurogenesis.

摘要

脑室下区(SVZ)来源的成年神经球表达两种外切核苷酸酶,即核苷三磷酸二磷酸水解酶2(NTPDase2)和组织非特异性碱性磷酸酶(TNAP)。核苷酸受体P2Y(1)和P2Y(2)的激动剂以及腺苷可增强生长因子介导的祖细胞增殖。NTPDase2分别将ATP和UTP转化为ADP和UDP,它们都是P2Y受体激动剂。TNAP水解核苷三磷酸和二磷酸并产生P1受体激动剂腺苷。在SVZ中,NTPDase2由B型细胞特异性表达。为了进一步研究嘌呤能信号通路的关键分子与神经发生区域的关联,我们分析了成年和发育中小鼠脑侧脑室中TNAP的表达。在成年脑中,TNAP由SVZ的B型、A型和至少部分C型细胞表达,并贯穿于吻侧迁移流。成年SVZ中几乎100%增殖的、Ki-67阳性细胞对TNAP呈染色阳性,支持TNAP与SVZ祖细胞普遍相关的观点。相比之下,齿状回中NTPDase2阳性祖细胞为TNAP阴性。在胚胎第14天(E14)时,端脑泡的基本上所有细胞都显示出TNAP活性,包括双皮质素阳性神经母细胞。在胚胎进一步发育过程中,增强的TNAP活性局限于脑室和SVZ的细胞。与TNAP不同,NTPDase2在出生前后首次在SVZ中表达,与TNAP阳性的SVZ边界细胞相关。在后期发育过程中,NTPDase2阳性细胞从脑室表面消失,并开始在脑室下双皮质素阳性细胞簇周围形成鞘,显然转变为B型细胞。我们的结果确定TNAP和NTPDase2为成年和发育中小鼠脑中祖细胞亚群的新型标志物。它们进一步支持了通过细胞外核苷酸和核苷进行信号传导有助于胚胎和成年神经发生的观点。

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