MicroRNA-133b Negatively Regulates Zebrafish Single Mauthner-Cell Axon Regeneration through Targeting tppp3 in Vivo.
MicroRNA-133b Negatively Regulates Zebrafish Single Mauthner-Cell Axon Regeneration through Targeting tppp3 in Vivo.
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MicroRNA-133b 通过体内靶向 tppp3 负调控斑马鱼单 Mauthner 细胞轴突再生
DOI：
10.3389/fnmol.2017.00375
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发表时间：
2017
影响因子：
4.8
通讯作者：
Hu B
中科院分区：
文献类型：
--
作者：
Huang R;Chen M;Yang L;Wagle M;Guo S;Hu B
轴突再生是神经修复和功能恢复的基础，依赖于可归因于microRNA（miRNA）调节的基因表达的快速变化。MiR-133 b已被证实在斑马鱼不同器官再生中发挥重要作用，但其在体内调控轴突再生的作用仍存在争议。在这里，结合单细胞电穿孔与基于载体的miRNA表达系统，我们在斑马鱼的单细胞水平上调节了Mauthner细胞（M细胞）中miR-133 b的表达。通过体内成像，我们发现miR-133 b的过表达抑制轴突再生，而miR-133 b的下调促进轴突生长。我们进一步表明，miR-133 b通过直接靶向一个新的再生相关基因tppp 3来调节轴突再生，该基因属于微管蛋白聚合促进蛋白家族。tppp 3功能获得或丧失实验表明tppp 3是一个可以促进轴突再生的新基因。此外，我们观察到线粒体运动性的减少，这已被确定为与轴突再生的正相关，在miR-133 b过表达的M细胞。综上所述，我们的工作提供了一种新的方法来研究miRNA在单个细胞中的作用，并建立了miR-133 b在斑马鱼M细胞轴突再生中的关键细胞自主作用。我们提出上调新发现的再生相关基因tppp 3可能会增强轴突再生。
Axon regeneration, fundamental to nerve repair, and functional recovery, relies on rapid changes in gene expression attributable to microRNA (miRNA) regulation. MiR-133b has been proved to play an important role in different organ regeneration in zebrafish, but its role in regulating axon regeneration in vivo is still controversial. Here, combining single-cell electroporation with a vector-based miRNA-expression system, we have modulated the expression of miR-133b in Mauthner-cells (M-cells) at the single-cell level in zebrafish. Through in vivo imaging, we show that overexpression of miR-133b inhibits axon regeneration, whereas down-regulation of miR-133b, promotes axon outgrowth. We further show that miR-133b regulates axon regeneration by directly targeting a novel regeneration-associated gene, tppp3, which belongs to Tubulin polymerization-promoting protein family. Gain or loss-of-function of tppp3 experiments indicated that tppp3 was a novel gene that could promote axon regeneration. In addition, we observed a reduction of mitochondrial motility, which have been identified to have a positive correlation with axon regeneration, in miR-133b overexpressed M-cells. Taken together, our work provides a novel way to study the role of miRNAs in individual cell and establishes a critical cell autonomous role of miR-133b in zebrafish M-cell axon regeneration. We propose that up-regulation of the newly founded regeneration-associated gene tppp3 may enhance axonal regeneration.
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影响因子：
16.6
作者：
Canty, A. J.;Huang, L.;De Paola, V.
通讯作者：
De Paola, V.
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影响因子：
48
作者：
Ebert, Margaret S.;Neilson, Joel R.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.
影响因子：
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作者：
Hoppe B;Pietsch S;Franke M;Engel S;Groth M;Platzer M;Englert C
通讯作者：
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