Chapouton Prisca, Adolf Birgit, Leucht Christoph, Tannhäuser Birgit, Ryu Soojin, Driever Wolfgang, Bally-Cuif Laure
Zebrafish Neurogenetics Junior Research Group, Institute of Virology, Technical University-Munich, Trogerstrasse 4b, D-81675, Munich, Germany.
Development. 2006 Nov;133(21):4293-303. doi: 10.1242/dev.02573.
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.
目前脊椎动物成年神经干细胞模型主要局限于啮齿动物的前脑。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/或脑区中鉴定新的成年干细胞群体。硬骨鱼斑马鱼似乎是一个理想的系统，因为成年斑马鱼大脑中的细胞增殖龛比哺乳动物大脑中的多得多。作为在该系统中鉴定干细胞群体的起点，我们使用了一种胚胎神经干细胞标记物，即E(spl) bHLH转录因子Her5。我们证明，her5的表达不仅限于胚胎神经祖细胞，还在成年斑马鱼大脑中定义了中脑和后脑交界处的一个新的增殖区。我们表明，成年her5表达细胞增殖缓慢、自我更新并表达神经干细胞标记物。最后，通过在her5:gfp转基因动物中进行体内谱系追踪，我们证明her5阳性群体具有多能性，原位产生分化的神经元和胶质细胞，这些细胞分布在基底中脑。我们的研究结果最终在完整的脊椎动物大脑中鉴定出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。这个位于前脑之外的细胞群体为评估脊椎动物神经干细胞生物学的一般机制提供了一个有力的模型。此外，这个细胞群体的第一个转录因子特征Her5表明，E(Spl)是一个有前途的成年神经干细胞调节因子候选家族。
