Department of Molecular Embryology, University of Freiburg, D-79104 Freiburg, Germany.
J Comp Neurol. 2012 Jun 1;520(8):1650-62. doi: 10.1002/cne.23004.
Thymosin β4 (Tβ4) is a highly conserved G-actin binding polypeptide with multiple intra- and extracellular functions. While stem-cell activation as well as promotion of cell survival and migration by Tβ4 have been investigated in various in vitro and in vivo studies, there are few data on the implications of Tβ4 in brain development. In the present study we analyzed Tβ4 expression in the developing optic tectum of the chicken (Gallus domesticus) and performed in ovo retroviral transduction and plasmid electroporation for overexpression and knockdown of Tβ4. We found marked Tβ4 expression in the tectal plate and in all neuronal layers of later developmental stages, but not in the ventricular zone where neural stem cells reside and divide. Knockdown of Tβ4 inhibited growth of Tβ4-depleted hemispheres, whereas overexpression of Tβ4 led to the production of neuroepithelial folds resembling gyri and sulci, which are not normally present in avian brains. The mechanism yielding enhanced growth of Tβ4 overexpressing hemispheres involved enhanced proliferation, thus indicating an impact of Tβ4 on the neural stem cell and/or progenitor cell population. In summary, we found that due to its effects on proliferation, Tβ4 expression has a large impact on neuroepithelial and macroscopic brain development.
胸腺素β4（Tβ4）是一种高度保守的 G-肌动蛋白结合多肽，具有多种细胞内和细胞外功能。虽然 Tβ4 在各种体外和体内研究中已被证明具有激活干细胞以及促进细胞存活和迁移的作用，但关于 Tβ4 在大脑发育中的作用的数据却很少。在本研究中，我们分析了鸡（Gallus domesticus）发育中的视顶盖中 Tβ4 的表达，并进行了胚胎病毒转导和质粒电穿孔以过表达和敲低 Tβ4。我们发现 Tβ4 在发育后期的 tectal 板和所有神经元层中均有明显表达，但在神经干细胞所在和分裂的脑室区没有表达。Tβ4 的敲低抑制了 Tβ4 耗尽半球的生长，而 Tβ4 的过表达导致了类似于脑回和脑沟的神经上皮褶皱的产生，而鸟类大脑中通常没有这些结构。导致 Tβ4 过表达半球生长增强的机制涉及到增殖的增强，这表明 Tβ4 对神经干细胞和/或祖细胞群体有影响。总之，我们发现由于其对增殖的影响，Tβ4 的表达对神经上皮和大脑宏观发育有很大的影响。
