Kuo Ting-Yu, Hong Chen-Jei, Hsueh Yi-Ping
Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, 11221, Taiwan.
Mol Cell Neurosci. 2009 Nov;42(3):195-207. doi: 10.1016/j.mcn.2009.07.006. Epub 2009 Jul 17.
The extension of axon branches is important for target innervation but how axon branching is regulated is currently not well understood. Here, we report that Bcl11A/CTIP1/Evi9, a zinc finger transcription factor, downregulates axon branching. Knockdown of Bcl11A induced axon branching and multi-axon formation, as well as dendrite outgrowth. Due to alternative splicing, a single Bcl11A gene encodes two protein products, Bcl11A-L and -S. Bcl11A-L was found to be the main Bcl11A player in regulation of neurite arborization; Bcl11A-S is an antagonist of Bcl11A-L. Time-lapse study further suggests that Bcl11A-L knockdown enhances axon dynamics and increases the duration of axon outgrowth. Finally, the expression of DCC and MAP1b, two molecules involved in direction and branching of axon outgrowth, is controlled by Bcl11A-L. DCC overexpression rescues the phenotype induced by Bcl11A-L knockdown. In conclusion, this report provides the first evidence that Bcl11A is important for neurite arborization.
轴突分支的延伸对于靶神经支配很重要，但目前对轴突分支如何被调控还了解得不够透彻。在此，我们报告锌指转录因子Bcl11A/CTIP1/Evi9可下调轴突分支。敲低Bcl11A会诱导轴突分支和多轴突形成，以及树突生长。由于可变剪接，单个Bcl11A基因编码两种蛋白质产物，即Bcl11A-L和Bcl11A-S。研究发现Bcl11A-L是Bcl11A调控神经突分支的主要作用形式；Bcl11A-S是Bcl11A-L的拮抗剂。延时研究进一步表明，敲低Bcl11A-L可增强轴突动态变化并延长轴突生长的持续时间。最后，轴突生长方向和分支所涉及的两个分子DCC和MAP1b的表达受Bcl11A-L调控。过表达DCC可挽救由敲低Bcl11A-L所诱导的表型。总之，本报告首次提供证据表明Bcl11A对神经突分支很重要。
