tec-1 kinase negatively regulates regenerative neurogenesis in planarians
tec-1 kinase negatively regulates regenerative neurogenesis in planarians
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DOI：
10.7554/elife.47293
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发表时间：
2020-01-20
期刊：
影响因子：
7.7
通讯作者：
Petersen, Christian P.
中科院分区：
文献类型：
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作者：
Karge, Alexander;Bonar, Nicolle A.;Petersen, Christian P.
成人神经发生的负性调节因子作为促进神经元修复的靶点特别感兴趣，但还很少有人被发现。浮游生物可以使用多能的成体干细胞再生整个中枢神经系统，这个过程受到强有力的调控，以确保新神经元的产生是适当的丰富。使用高通量管道对大脑化学感受性神经元进行量化，我们发现保守的酪氨酸激酶tec-1是脊椎动物神经元再生的负调控因子。Tec-1RNAi增加了通过内稳态再生或维持的几种CNS和PNS神经元亚型的丰度，而不影响身体构型或非神经细胞。使用TUNEL、BrdU、祖细胞标记和再生过程中干细胞消除的实验表明，tec-1限制了新分化神经元的存活。在脊椎动物中，Tec激酶家族在免疫功能中的作用已被广泛研究，我们的结果确定了tec-1作为脊椎动物成体神经发生的负调节因子的新角色。
Negative regulators of adult neurogenesis are of particular interest as targets to enhance neuronal repair, but few have yet been identified. Planarians can regenerate their entire CNS using pluripotent adult stem cells, and this process is robustly regulated to ensure that new neurons are produced in proper abundance. Using a high-throughput pipeline to quantify brain chemosensory neurons, we identify the conserved tyrosine kinase tec-1 as a negative regulator of planarian neuronal regeneration. tec-1RNAi increased the abundance of several CNS and PNS neuron subtypes regenerated or maintained through homeostasis, without affecting body patterning or non-neural cells. Experiments using TUNEL, BrdU, progenitor labeling, and stem cell elimination during regeneration indicate tec-1 limits the survival of newly differentiated neurons. In vertebrates, the Tec kinase family has been studied extensively for roles in immune function, and our results identify a novel role for tec-1 as negative regulator of planarian adult neurogenesis.