Tuba1a 基因的表达受 KLF6/7 调控，对于斑马鱼中枢神经系统的发育和再生是必需的。
Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish.
机构信息
Neuroscience Program, University of Michigan, Biomedical Sciences Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
出版信息
Mol Cell Neurosci. 2010 Apr;43(4):370-83. doi: 10.1016/j.mcn.2010.01.004. Epub 2010 Feb 1.
Abstract
We report that knockdown of the alpha1 tubulin isoform Tuba1a, but not the highly related Tuba1b, dramatically impedes nervous system formation during development and RGC axon regeneration following optic nerve injury in adults. Within the tuba1a promoter, a G/C-rich element was identified that is necessary for tuba1a induction during RGC differentiation and optic axon regeneration. KLF6a and 7a, which we previously reported are essential for optic axon regeneration (Veldman et al., 2007), bind this G/C-rich element and transactivate the tuba1a promoter. In vivo knockdown of KLF6a and 7a attenuate regeneration-dependent activation of the endogenous tuba1a and p27 genes. These results suggest tuba1a expression is necessary for CNS development and regeneration and that KLF6a and 7a mediate their effects, at least in part, via transcriptional control of tuba1a promoter activity.
摘要
我们报告称，敲低α1 微管蛋白同工型 Tuba1a（而非高度相关的 Tuba1b），可在发育过程中显著阻碍神经系统的形成，并在成年视神经损伤后抑制 RGC 轴突再生。在 tuba1a 启动子中，鉴定出一个富含 G/C 的元件，该元件对于 RGC 分化和视神经轴突再生过程中 tuba1a 的诱导是必需的。KLF6a 和 7a 先前被报道对于视神经轴突再生是必需的（Veldman 等人，2007），它们结合该富含 G/C 的元件并反式激活 tuba1a 启动子。体内敲低 KLF6a 和 7a 可减弱再生依赖性的内源性 tuba1a 和 p27 基因的激活。这些结果表明 tuba1a 表达对于中枢神经系统的发育和再生是必需的，并且 KLF6a 和 7a 通过转录控制 tuba1a 启动子活性至少部分介导其作用。
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