Zaki Paulette A, Martynoga Ben, Delafield-Butt Jonathan T, Fotaki Vassiliki, Yu Tian, Price David J
Genes and Development Group, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK.
Eur J Neurosci. 2005 Sep;22(6):1547-51. doi: 10.1111/j.1460-9568.2005.04323.x.
The transcription factor Gli3 is important for brain and limb development. Mice homozygous for a mutation in Gli3 (Gli3Xt/Xt) have severe abnormalities of telencephalic development and previous studies have suggested that aberrant cell death may contribute to the Gli3Xt/Xt phenotype. We demonstrate that telencephalic cells from embryonic Gli3Xt/Xt embryos survive better and are more resistant to death induced by cytosine arabinoside, a nucleoside analogue that induces death in neuronal progenitors and neurons, than are control counterparts in vitro. Culture medium conditioned by Gli3Xt/Xt cells is more effective at enhancing the viability of control telencephalic cells than medium conditioned by control cells, indicating that Gli3Xt/Xt cells release a factor or factors which enhance telencephalic cell viability. Gli3(Xt/Xt) cells are also more sensitive to released factors present in conditioned media. These data suggest that Gli3 plays both cell-autonomous and cell-nonautonomous roles in mediating telencephalic cell viability.
转录因子Gli3对大脑和肢体发育至关重要。Gli3发生突变的纯合子小鼠（Gli3Xt/Xt）存在严重的端脑发育异常，先前的研究表明异常细胞死亡可能导致Gli3Xt/Xt表型。我们证明，与体外对照细胞相比，来自胚胎Gli3Xt/Xt胚胎的端脑细胞存活得更好，并且对阿糖胞苷诱导的死亡更具抵抗力，阿糖胞苷是一种核苷类似物，可诱导神经元祖细胞和神经元死亡。Gli3Xt/Xt细胞条件培养基比对照细胞条件培养基在增强对照端脑细胞活力方面更有效，这表明Gli3Xt/Xt细胞释放一种或多种增强端脑细胞活力的因子。Gli3(Xt/Xt)细胞对条件培养基中存在的释放因子也更敏感。这些数据表明，Gli3在介导端脑细胞活力方面发挥细胞自主和非细胞自主作用。
