Cho Jang-Hyeon, Tsai Ming-Jer
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dev Biol. 2006 Feb 1;290(1):125-38. doi: 10.1016/j.ydbio.2005.11.024. Epub 2005 Dec 20.
BETA2/NeuroD1 has been shown to play a major role in terminal differentiation of the pancreatic and enteroendocrine cells, as well as for the survival of photoreceptors. Here, we report that the loss of BETA2/NeuroD1 affected the cerebellar development with a major reduction of granule cell number. However, there is a differential reduction of granule cells along the anterior and posterior axis of the cerebellum; while the reduction of granule cells in the anterior lobes is substantial, there is an almost complete loss of granule cells in the posterior compartment. To understand the mechanism for this anterior-posterior difference, we carried out detailed analyses. We found that both BETA2/NeuroD1 and its direct target TrkC, expression commence earlier in the posterior part than those in the anterior part during cerebellum development. Consequently, loss of BETA2/NeuroD1 enhances granule cell death in the posterior 2 days earlier than the anterior. Furthermore, the higher rate of cell death in the posterior of the cerebellum is concomitant with the reduction of TrkC expression in knockout mice. Thus, our data indicate that preferential expression of BETA2/NeuroD1 and TrkC in posterior lobes explains the earlier start of cell apoptosis and preferential loss of granule cells in the posterior lobes.
β2/NeuroD1已被证明在胰腺和肠内分泌细胞的终末分化以及光感受器的存活中起主要作用。在此，我们报告β2/NeuroD1的缺失影响小脑发育，颗粒细胞数量大幅减少。然而，沿小脑前后轴的颗粒细胞减少存在差异；前叶颗粒细胞减少显著，而后部区域的颗粒细胞几乎完全丧失。为了解这种前后差异的机制，我们进行了详细分析。我们发现，在小脑发育过程中，β2/NeuroD1及其直接靶点TrkC的表达在后部比在前部开始得更早。因此，β2/NeuroD1的缺失比在前部提前2天增强了后部颗粒细胞的死亡。此外，小脑后部较高的细胞死亡率与基因敲除小鼠中TrkC表达的减少同时出现。因此，我们的数据表明，β2/NeuroD1和TrkC在后叶的优先表达解释了细胞凋亡的较早开始以及后叶颗粒细胞的优先丧失。
