Liu Y, Montell D J
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
Development. 2001 Feb;128(3):321-30. doi: 10.1242/dev.128.3.321.
Epithelial to mesenchymal transitions and cell migration are important features of embryonic development and tumor metastasis. We are employing a systematic genetic approach to study the border cells in the Drosophila ovary, as a simple model for these cellular behaviors. Previously we found that expression of the basic-region/leucine zipper transcription factor, C/EBP, is required for the border cells to initiate their migration. Here we report the identification of a second nuclear factor, named JING (which means 'still'), that is required for initiation of border cell migration. The jing locus was identified in a screen for mutations that cause border cell migration defects in mosaic clones. The jing mutant phenotype resembles that of slbo mutations, which disrupt the Drosophila C/EBP gene, but is distinct from other classes of border cell migration mutants. Expression of a jing-lacZ reporter in border cells requires C/EBP. Moreover, expression of jing from a heat-inducible promoter rescues the border cell migration defects of hypomorphic slbo mutants. The JING protein is most closely related to a mouse protein, AEBP2, which was identified on the basis of its ability to bind a small regulatory sequence within the adipocyte AP2 gene to which mammalian C/EBP also binds. We propose that the need to coordinate cell differentiation with nutritional status may be the link between mammalian adipocytes and Drosophila border cells that led to the conservation of C/EBP and AEBP2.
上皮细胞向间充质细胞的转变以及细胞迁移是胚胎发育和肿瘤转移的重要特征。我们正在采用一种系统的遗传学方法来研究果蝇卵巢中的边界细胞,以此作为这些细胞行为的一个简单模型。此前我们发现,碱性区域/亮氨酸拉链转录因子C/EBP的表达是边界细胞启动迁移所必需的。在此我们报告鉴定出了第二种核因子,名为JING(意为“静止”),它是边界细胞迁移启动所必需的。jing基因座是在对导致镶嵌克隆中边界细胞迁移缺陷的突变进行筛选时鉴定出来的。jing突变体表型类似于slbo突变体,后者破坏了果蝇C/EBP基因,但与其他类别的边界细胞迁移突变体不同。边界细胞中jing - lacZ报告基因的表达需要C/EBP。此外,从热诱导启动子表达jing可挽救低表达slbo突变体的边界细胞迁移缺陷。JING蛋白与一种小鼠蛋白AEBP2关系最为密切,AEBP2是根据其结合脂肪细胞AP2基因内一个小调控序列的能力而鉴定出来的,哺乳动物C/EBP也能结合该序列。我们提出,将细胞分化与营养状况相协调的需求可能是哺乳动物脂肪细胞与果蝇边界细胞之间的联系,这导致了C/EBP和AEBP2的保守性。