Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication.
Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication.
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DOI：
10.7554/elife.58756
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发表时间：
2021-02-02
期刊：
影响因子：
7.7
通讯作者：
Hidalgo A
中科院分区：
文献类型：
--
作者：
Harrison NJ;Connolly E;Gascón Gubieda A;Yang Z;Altenhein B;Losada Perez M;Moreira M;Sun J;Hidalgo A
了解中枢神经系统损伤如何诱导动物神经新生，将有助于促进人类神经再生。再生神经发生可能起源于胶质细胞和胶质神经元-胶质抗原-2 （NG2）可能感知损伤诱导的神经元信号，但这些尚不清楚。在这里，我们使用果蝇来寻找与NG2同源物kon-tiki （kon）功能相关的基因，并鉴定了神经元分泌胰岛素所需的胰岛抗原-2 （Ia-2）。ia-2缺失和过表达均可诱导神经干细胞基因表达，损伤可增加ia-2表达并诱导异位神经干细胞。通过遗传分析和谱系追踪，我们证明Ia-2和Kon调控果蝇胰岛素样肽6 （Dilp-6）诱导胶质细胞增殖和神经干细胞。异位神经干细胞可以分裂，有限的新生神经发生可以追溯到神经胶质细胞。总的来说，Ia-2和Dilp-6驱动神经-胶质细胞接力，恢复胶质细胞，并将胶质细胞重新编程为神经干细胞进行再生。
Understanding how injury to the central nervous system induces de novo neurogenesis in animals would help promote regeneration in humans. Regenerative neurogenesis could originate from glia and glial neuron-glia antigen-2 (NG2) may sense injury-induced neuronal signals, but these are unknown. Here, we used Drosophila to search for genes functionally related to the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Both loss and over-expression of ia-2 induced neural stem cell gene expression, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate Drosophila insulin-like peptide 6 (Dilp-6) to induce glial proliferation and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia and reprogrammes glia into neural stem cells for regeneration.
影响因子：
4.1
作者：
Nishimura, Takuya;Harashima, Shin-ichi;Hu Yafang;Notkins, Abner Louis
通讯作者：
Notkins, Abner Louis
影响因子：
3.3
作者：
Carmona GN;Nishimura T;Schindler CW;Panlilio LV;Notkins AL
通讯作者：
Notkins AL