Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA.
Dev Dyn. 2013 May;242(5):414-31. doi: 10.1002/dvdy.23926. Epub 2013 Feb 8.
Cell motility is essential for embryonic development and physiological processes such as the immune response, but also contributes to pathological conditions such as tumor progression and inflammation. However, our understanding of the mechanisms underlying migratory processes is incomplete. Drosophila border cells provide a powerful genetic model to identify the roles of genes that contribute to cell migration.
Members of the Hedgehog signaling pathway were uncovered in two independent screens for interactions with the small GTPase Rac and the polarity protein Par-1 in border cell migration. Consistent with a role in migration, multiple Hh signaling components were enriched in the migratory border cells. Interference with Hh signaling by several different methods resulted in incomplete cell migration. Moreover, the polarized distribution of E-Cadherin and a marker of tyrosine kinase activity were altered when Hh signaling was disrupted. Conservation of Hh-Rac and Hh-Par-1 signaling was illustrated in the wing, in which Hh-dependent phenotypes were enhanced by loss of Rac or par-1.
We identified a pathway by which Hh signaling connects to Rac and Par-1 in cell migration. These results further highlight the importance of modifier screens in the identification of new genes that function in developmental pathways.
细胞运动对于胚胎发育和生理过程（如免疫反应）至关重要，但也会导致病理状况（如肿瘤进展和炎症）。然而，我们对迁移过程背后的机制的理解并不完整。果蝇边缘细胞提供了一个强大的遗传模型，可以识别有助于细胞迁移的基因的作用。
在两个独立的筛选中，发现 Hedgehog 信号通路的成员与 Rac 小 GTPase 和极性蛋白 Par-1 相互作用，参与边缘细胞的迁移。与迁移作用一致，多种 Hh 信号通路成分在迁移的边缘细胞中富集。通过几种不同的方法干扰 Hh 信号通路会导致细胞迁移不完全。此外，当 Hh 信号通路被破坏时，E-Cadherin 的极化分布和酪氨酸激酶活性的标记物发生改变。Hh-Rac 和 Hh-Par-1 信号通路在翅膀中得到了保守，其中 Rac 或 par-1 的缺失增强了 Hh 依赖性表型。
我们确定了一条途径，通过该途径 Hh 信号通路在细胞迁移中连接到 Rac 和 Par-1。这些结果进一步强调了修饰筛选在鉴定发育途径中发挥作用的新基因中的重要性。
