Shi Wei-Yang, Skeath James B
Program in Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Dev Biol. 2004 Jun 1;270(1):106-21. doi: 10.1016/j.ydbio.2004.02.011.
The Bj1 gene encodes the Drosophila homolog of RCC1, the guanine-nucleotide exchange factor for RanGTPase. Here, we provide the first phenotypic characterization of a RCC1 homolog in a developmental model system. We identified Bj1 (dRCC1) in a genetic screen to identify mutations that alter central nervous system development. We find that zygotic dRCC1 mutant embryos exhibit specific defects in the development and differentiation of lateral CNS neurons although cell division and the cell cycle appear grossly normal. dRCC1 mutant nerve cords contain abnormally large cells with compartmentalized nuclei and exhibit increased transcription in the lateral CNS. As RCC1 is an important component of the nucleocytoplasmic transport machinery, we find that dRCC1 function is required for nuclear import of nuclear localization signal sequence (NLS)-carrying cargo molecules. Finally, we show that dRCC1 is required for cell proliferation and/or survival during germline, eye and wing development and that dRCC1 appears to facilitate apoptosis.
Bj1基因编码RCC1的果蝇同源物,RCC1是RanGTPase的鸟嘌呤核苷酸交换因子。在这里,我们首次在发育模型系统中对RCC1同源物进行了表型特征分析。我们在一项基因筛选中鉴定出Bj1(dRCC1),以识别改变中枢神经系统发育的突变。我们发现,合子型dRCC1突变胚胎在中枢神经系统外侧神经元的发育和分化中表现出特定缺陷,尽管细胞分裂和细胞周期看起来基本正常。dRCC1突变神经索含有异常大的细胞,细胞核呈分隔状,并且在中枢神经系统外侧表现出转录增加。由于RCC1是核质运输机制的重要组成部分,我们发现dRCC1功能是携带核定位信号序列(NLS)的货物分子进行核输入所必需的。最后,我们表明dRCC1在生殖系、眼睛和翅膀发育过程中对于细胞增殖和/或存活是必需的,并且dRCC1似乎促进细胞凋亡。