Regenerative Neurogenesis from Neural Progenitor Cells Requires Injury-Induced Expression of Gata3

Regenerative Neurogenesis from Neural Progenitor Cells Requires Injury-Induced Expression of Gata3
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DOI:
10.1016/j.devcel.2012.10.014
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发表时间:
2012-12-11
期刊:
影响因子:
11.8
通讯作者:
Brand, Michael
Brand, Michael
中科院分区:
生物学1区
文献类型:
--
作者:
Kizil, Caghan;Kyritsis, Nikos;Brand, Michael

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与哺乳动物不同,成年斑马鱼的大脑可以在损伤后再生,这是由于具有放射状胶质特征的干细胞的神经发生能力。我们假设损伤诱导的再生程序可能在斑马鱼脑损伤后启动,并使再生神经发生成为可能。在这里,我们确定了一个这样的基因转录因子gata3,它只在不同的斑马鱼器官损伤后表达。Gata3是放射状胶质细胞反应性增殖、随后的再生神经发生和新生神经元迁移所必需的。我们发现Gata3的这些再生特异性作用依赖于损伤,因为Gata3在未损伤的成年斑马鱼脑中的过表达不足以诱导神经发生。因此,gata3作为一个特定的损伤诱导的促再生因子,是脊椎动物的再生能力所必需的。
The adult zebrafish brain, unlike mammalian counterparts, can regenerate after injury owing to the neurogenic capacity of stem cells with radial glial character. We hypothesized that injury-induced regenerative programs might be turned on after injury in zebrafish brain and enable regenerative neurogenesis. Here we identify one such gene-the transcription factor gata3-which is expressed only after injury in different zebrafish organs. Gata3 is required for reactive proliferation of radial glia cells, subsequent regenerative neurogenesis, and migration of the newborn neurons. We found that these regeneration-specific roles of Gata3 are dependent on the injury because Gata3 overexpression in the unlesioned adult zebrafish brain is not sufficient to induce neurogenesis. Thus, gata3 acts as a specific injury-induced proregenerative factor that is essential for the regenerative capacity in vertebrates.