Wang Xuejiao, Bo Jinyan, Bridges Tina, Dugan Katherine D, Pan Tien-chi, Chodosh Lewis A, Montell Denise J
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Dev Cell. 2006 Apr;10(4):483-95. doi: 10.1016/j.devcel.2006.02.003.
Cell migration contributes to normal development and homeostasis as well as to pathological processes such as inflammation and tumor metastasis. Previous genetic screens have revealed signaling pathways that govern follicle cell migrations in the Drosophila ovary, but few downstream targets of the critical transcriptional regulators have been identified. To characterize the gene expression profile of two migratory cell populations and identify Slbo targets, we purified border cells and centripetal cells expressing the mouse CD8 antigen and carried out whole-genome microarray analysis. Genes predicted to control actin dynamics and the endocytic and secretory pathways were overrepresented in the migratory cell transcriptome. Mutations in five genes, including ttk, failed to complement previously isolated mutations that cause cell migration defects in mosaic clones. Functional analysis revealed a role for the Notch-activating protease Kuzbanian in border cell migration and identified Tie as a guidance receptor for the border cells.
细胞迁移有助于正常发育和体内平衡，以及诸如炎症和肿瘤转移等病理过程。先前的基因筛选已经揭示了调控果蝇卵巢中卵泡细胞迁移的信号通路，但关键转录调节因子的下游靶点却鲜有被鉴定出来。为了表征两个迁移细胞群体的基因表达谱并鉴定Slbo靶点，我们纯化了表达小鼠CD8抗原的边界细胞和向心细胞，并进行了全基因组微阵列分析。预测控制肌动蛋白动力学以及内吞和分泌途径的基因在迁移细胞转录组中过度富集。包括ttk在内的五个基因的突变不能互补先前在镶嵌克隆中分离出的导致细胞迁移缺陷的突变。功能分析揭示了Notch激活蛋白酶库兹班在边界细胞迁移中的作用，并确定Tie为边界细胞的导向受体。
