Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors
Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors
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DOI：
10.1002/glia.20654
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发表时间：
2008-06-01
期刊：
影响因子：
6.2
通讯作者：
Arenas, Ernest
中科院分区：
文献类型：
--
作者：
Bonilla, Sonia;Hall, Anita C.;Arenas, Ernest
底板（FP）是一个信号中心和富含放射状胶质样细胞的结构，传统上认为它缺乏神经元和神经元祖细胞。然而，在中脑中，FP包含多巴胺能（DA）谱系的神经元，需要与放射状胶质样细胞接触才能诱导。因此，我们决定探索DA神经发生过程中放射状胶质细胞与神经元之间的相互作用关系。利用一种新型的FP放射状胶质样细胞培养系统和逆转录病毒，在体外对DA神经元进行了谱系追踪。在子宫内，BrdU脉冲追踪广泛标记中脑FP，并在体内和FP培养中追踪DA神经元。此外，从E9.5到E13.5，中脑FP仅在神经上皮最顶端部分含有分裂细胞，这些细胞被鉴定为放射状胶质样细胞。因此，我们假设中脑FP放射状胶质样细胞可能是DA祖细胞，并在体内验证了我们的假设。在Tis21-EGFP敲入小鼠中对DA祖细胞与EGFP进行谱系追踪，以及在GLAST::CreERT2/ZEG小鼠中进行遗传命运定位，发现中脑FP的神经上皮，特别是GLAST+放射状胶质样细胞是DA祖细胞。综上所述，我们的实验支持了中脑FP不同于其他FP区域的概念，并证明中脑的FP径向胶质样细胞具有神经源性，并产生中脑DA神经元。(C) 2008 Wiley-Liss, Inc。
The floor plate (FP), a signaling center and a structure rich in radial glia-like cells, has been traditionally thought to be devoid of neurons and neuronal progenitors. However, in the midbrain, the FP contains neurons of the dopaminergic (DA) lineage that require contact with radial glia-like cells for their induction. We, therefore, decided to explore the interaction relationship between radial glia and neurons during DA neurogenesis. Taking advantage of a novel FP radial glia-like cell culture system and retroviruses, DA neurons were lineage traced in vitro. In utero BrdU pulse-chases extensively labeled the midbrain FP and traced DA neurons both in vivo and in FP cultures. Moreover, from E9.5 to E13.5 the midbrain FP contained dividing cells only in the most apical part of the neuroepithelium, in cells identified as radial glia-like cells. We, therefore, hypothesized that midbrain FP radial glia-like cells could be DA progenitors and tested our hypothesis in vivo. Lineage tracing of DA progenitors with EGFP in Tis21-EGFP knock-in mice, and genetic fate mapping in GLAST::CreERT2/ZEG mice identified the neuroepithelium of the midbrain FP, and specifically, GLAST+ radial glia-like cells as DA progenitors. Combined, our experiments support the concept that the midbrain FP differs from other FP regions and demonstrate that FP radial glia-like cells in the midbrain are neurogenic and give rise to midbrain DA neurons. (C) 2008 Wiley-Liss, Inc.