Department of the Regulation of Genetic Processes, Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Faculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2020 Oct 10;21(20):7468. doi: 10.3390/ijms21207468.
Collective cell migration is a complex process that happens during normal development of many multicellular organisms, as well as during oncological transformations. In oogenesis, a small set of follicle cells originally located at the anterior tip of each egg chamber become motile and migrate as a cluster through nurse cells toward the oocyte. These specialized cells are referred to as border cells (BCs) and provide a simple and convenient model system to study collective cell migration. The process is known to be complexly regulated at different levels and the product of the () gene, the C/EBP transcription factor, is one of the key elements in this process. However, little is known about the regulation of expression. On the other hand, the ubiquitously expressed transcription factor GAGA, which is encoded by the () gene was previously demonstrated to be important for oogenesis. Here, we found that mutations cause substantial defects in BC migration. Partially, these defects are explained by the reduced level of expression in BCs. Additionally, a strong genetic interaction between and mutants, along with the presence of putative GAGA binding sites within the promoter and enhancer, suggests the direct regulation of this gene by GAGA. This idea is supported by the reduction in the -Gal4-driven GFP expression within BC clusters in mutant background. However, the inability of overexpression to compensate defects in BC migration caused by mutations suggests that there are other GAGA target genes contributing to this process. Taken together, the results define GAGA as another important regulator of BC migration in oogenesis.
细胞集体迁移是一个复杂的过程,发生在许多多细胞生物的正常发育过程中,以及肿瘤转化过程中。在卵子发生过程中,一小部分滤泡细胞最初位于每个卵室的前端变得运动,并作为一个集群通过滋养细胞向卵母细胞迁移。这些特化的细胞被称为边界细胞(BC),提供了一个简单方便的模型系统来研究细胞集体迁移。这个过程在不同的水平上被复杂地调节,并且()基因的产物,C/EBP 转录因子,是这个过程中的关键要素之一。然而,关于()表达的调节知之甚少。另一方面,普遍表达的转录因子 GAGA,由()基因编码,先前被证明对卵子发生很重要。在这里,我们发现()突变导致 BC 迁移的严重缺陷。部分原因是 BC 中()表达水平降低。此外,()和()突变体之间存在强烈的遗传相互作用,以及()启动子和增强子内存在假定的 GAGA 结合位点,表明该基因受到 GAGA 的直接调节。这个想法得到了在()突变体背景下 -Gal4 驱动 GFP 表达在 BC 簇中减少的支持。然而,()过表达不能补偿()突变导致的 BC 迁移缺陷,表明还有其他 GAGA 靶基因参与这个过程。总之,这些结果将 GAGA 定义为卵子发生中 BC 迁移的另一个重要调节剂。