her5 expression reveals a pool of neural stem cells in the adult zebrafish midbrain
her5 expression reveals a pool of neural stem cells in the adult zebrafish midbrain
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DOI：
10.1242/dev.02573
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发表时间：
2006-11-01
期刊：
影响因子：
4.6
通讯作者：
Bally-Cuif, Laure
中科院分区：
文献类型：
--
作者：
Chapouton, Prisca;Adolf, Birgit;Bally-Cuif, Laure
目前脊椎动物成体神经干细胞的模型主要限于啮齿动物前脑。为了提取神经干细胞生物学的一般机制，我们试图在其他模型系统和/或大脑区域中识别新的成体干细胞群。硬骨鱼斑马鱼似乎是一个理想的系统，因为成年斑马鱼脑中的细胞增殖比哺乳动物脑中的细胞增殖多得多。作为在该系统中识别干细胞群体的起点，我们使用胚胎神经干细胞标记物E（spl）bHLH转录因子Her 5。我们证明，her 5的表达不仅限于胚胎神经祖细胞，而且还定义了在成年斑马鱼大脑中，在中间和后脑之间的交界处的一个新的增殖区。我们发现，成人her 5表达细胞增殖缓慢，自我更新和表达神经干细胞标记。最后，使用在her 5：gfp转基因动物体内谱系追踪，我们证明her 5阳性的人口是多能的，在原位产生分化的神经元和胶质细胞，填充基底中脑。我们的研究结果最终确定了一个新的成年神经干细胞群体，以及它们的命运和内源性环境，在完整的脊椎动物大脑。这个位于前脑外的细胞群提供了一个强大的模型来评估脊椎动物神经干细胞生物学的一般机制。此外，该细胞群的第一个转录因子特征Her 5指向E（Spl）作为候选成体神经干细胞调节因子的有希望的家族。
Current models of vertebrate adult neural stem cells are largely restricted to the rodent forebrain. To extract the general mechanisms of neural stem cell biology, we sought to identify new adult stem cell populations, in other model systems and/or brain areas. The teleost zebrafish appears to be an ideal system, as cell proliferation in the adult zebrafish brain is found in many more niches than in the mammalian brain. As a starting point towards identifying stem cell populations in this system, we used an embryonic neural stem cell marker, the E(spl) bHLH transcription factor Her5. We demonstrate that her5 expression is not restricted to embryonic neural progenitors, but also defines in the adult zebrafish brain a new proliferation zone at the junction between the mid- and hindbrain. We show that adult her5-expressing cells proliferate slowly, self-renew and express neural stem cell markers. Finally, using in vivo lineage tracing in her5: gfp transgenic animals, we demonstrate that the her5-positive population is multipotent, giving rise in situ to differentiated neurons and glia that populate the basal midbrain. Our findings conclusively identify a new population of adult neural stem cells, as well as their fate and their endogenous environment, in the intact vertebrate brain. This cell population, located outside the forebrain, provides a powerful model to assess the general mechanisms of vertebrate neural stem cell biology. In addition, the first transcription factor characteristic of this cell population, Her5, points to the E(Spl) as a promising family of candidate adult neural stem cell regulators.