Stem Cells in the Adult Zebrafish Cerebellum: Initiation and Maintenance of a Novel Stem Cell Niche
Stem Cells in the Adult Zebrafish Cerebellum: Initiation and Maintenance of a Novel Stem Cell Niche
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DOI：
10.1523/jneurosci.0072-09.2009
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发表时间：
2009-05-13
影响因子：
5.3
通讯作者：
Brand, Michael
中科院分区：
文献类型：
--
作者：
Kaslin, Jan;Ganz, Julia;Brand, Michael
在成人中枢神经系统中，神经发生发生在特殊的环境中。目前尚不清楚这些生态位在发育过程中是如何形成以及如何维持的。与哺乳动物相比，斑马鱼的干细胞生态位丰富，并且在端脑以外的大脑其他部位也有发现。为了了解脊椎动物神经干细胞生态位的共同特征，我们利用转基因系、体内成像和标记分析研究了以前未知的干细胞生态位的起源和结构。我们发现双能干细胞维持在成年斑马鱼小脑的独特生态位中。值得注意的是，干细胞不是典型的神经胶质细胞，而是保留了神经上皮特征。小脑干细胞生态位是通过脑室和菱形唇祖细胞在涉及形态发生运动和组织生长的两步过程中协调位移而产生的。重要的是，微环境及其干细胞仍然通过以前未知的心室衍生物保持与心室接触。心室中增殖的因子被认为是干细胞活性的重要调节因子。为了测试一类重要因子（成纤维细胞生长因子）的需求，我们使用具有诱导型显性失活 Fgf 受体的斑马鱼。 Fgf 信号传导的抑制会导致干细胞活性显着降低。与主流观点相反，非哺乳动物脊椎动物中的成体神经干细胞表现出更多的神经上皮特征而不是神经胶质特征。然而，保留的上皮特性，例如不同的极化和心室接触，是维持脊椎动物神经干细胞活性的关键共同决定因素。
In the adult CNS, neurogenesis takes place in special niches. It is not understood how these niches are formed during development and how they are maintained. In contrast to mammals, stem cell niches are abundant in zebrafish and also found in other parts of the brain than telencephalon. To understand common characteristics of neural stem cell niches in vertebrates, we studied the origin and architecture of a previously unknown stem cell niche using transgenic lines, in vivo imaging, and marker analysis. We show that bipotent stem cells are maintained in a distinct niche in the adult zebrafish cerebellum. Remarkably, the stem cells are not typical glia but instead retain neuroepithelial characteristics. The cerebellar stem cell niche is generated by the coordinated displacement of ventricle and rhombic lip progenitors in a two-step process involving morphogenetic movements and tissue growth. Importantly, the niche and its stem cells still remain in ventricular contact through a previously unknown derivative of the ventricle. Factors propagated in the ventricle are thought to be important regulators of stem cell activity. To test the requirements of one family of important factors, Fibroblast growth factors, we used zebrafish with an inducible dominant-negative Fgf receptor. Inhibition of Fgf signaling leads to significant reduction of stem cell activity. In contrast to the predominant view, adult neural stem cells in nonmammalian vertebrates show more neuroepithelial than glial characteristics. Nevertheless, retained epithelial properties such as distinct polarization and ventricular contact are critical common determinants to maintain neural stem cell activity in vertebrates.