Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON, M5S 3G5, Canada.
Development. 2013 Jul;140(13):2808-17. doi: 10.1242/dev.089896. Epub 2013 May 29.
Border cell cluster (BCC) migration in the Drosophila ovary is an excellent system to study the gene regulatory network that enables collective cell migration. Here, we identify the large Maf transcription factor Traffic jam (Tj) as an important regulator of BCC migration. Tj has a multifaceted impact on the known core cascade that enables BCC motility, consisting of the Jak/Stat signaling pathway, the C/EBP factor Slow border cells (Slbo), and the downstream effector DE-cadherin (DEcad). The initiation of BCC migration coincides with a Slbo-dependent decrease in Tj expression. This reduction of Tj is required for normal BCC motility, as high Tj expression strongly impedes migration. At high concentration, Tj has a tripartite negative effect on the core pathway: a decrease in Slbo, an increase in the Jak/Stat inhibitor Socs36E, and a Slbo-independent reduction of DEcad. However, maintenance of a low expression level of Tj in the BCC during migration is equally important, as loss of tj function also results in a significant delay in migration concomitant with a reduction of Slbo and consequently of DEcad. Taken together, we conclude that the regulatory feedback loop between Tj and Slbo is necessary for achieving the correct activity levels of migration-regulating factors to ensure proper BCC motility.
果蝇卵巢中的边缘细胞簇 (BCC) 迁移是研究允许细胞集体迁移的基因调控网络的绝佳系统。在这里，我们确定了大 Maf 转录因子 Traffic jam (Tj) 是 BCC 迁移的重要调节因子。Tj 对已知的核心级联反应有多种影响，该级联反应使 BCC 运动成为可能，包括 Jak/Stat 信号通路、C/EBP 因子 Slow border cells (Slbo) 和下游效应物 DE-cadherin (DEcad)。BCC 迁移的起始与 Tj 表达的 Slbo 依赖性降低相吻合。这种 Tj 的减少对于正常的 BCC 运动是必需的，因为高 Tj 表达强烈阻碍迁移。在高浓度下，Tj 对核心途径具有三重负面影响：Slbo 减少、Jak/Stat 抑制剂 Socs36E 增加以及 Slbo 独立的 DEcad 减少。然而，在迁移过程中 BCC 中 Tj 的低表达水平的维持同样重要，因为 tj 功能的丧失也会导致迁移明显延迟，同时 Slbo 减少，进而 DEcad 减少。总之，我们得出结论，Tj 和 Slbo 之间的调节反馈环对于达到调节迁移的因子的正确活性水平以确保适当的 BCC 运动是必要的。
