On the role of PDZ domain-encoding genes in Drosophila border cell migration.
On the role of PDZ domain-encoding genes in Drosophila border cell migration.
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DOI：
10.1534/g3.112.004093
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发表时间：
2012-11
期刊：
影响因子：
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通讯作者：
McDonald JA
中科院分区：
文献类型：
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作者：
Aranjuez G;Kudlaty E;Longworth MS;McDonald JA
在正常的胚胎发育和伤口愈合期间，细胞通常作为集体移动，尽管控制这种类型迁移的机制尚不清楚。果蝇黑腹果蝇的边缘细胞在卵子发生后期以簇的形式迁移，是一个强大的体内集体细胞迁移的遗传模型。为了发现参与边界细胞迁移的新基因，在编码PDZ结构域蛋白的66个基因中，被系统地通过体内RNAi敲除来定位。PDZ结构域是真核生物中发现的最大的蛋白质相互作用结构域家族之一。含有PDZ结构域的蛋白质参与多种生物学过程，包括信号转导和上皮尖-基极性的建立。以PDZ蛋白为靶点通过蛋白质复合体和这些蛋白质发挥作用的途径有效地评估了更多的基因。PAR-6是一种已知的边界细胞迁移调节因子，它是一种积极的成功，因此验证了这种方法。14个PDZ结构域基因的敲除中断了与多个RNAi系的迁移。候选基因具有不同的预测细胞功能，有望为控制边界细胞运动的机制提供新的见解。作为对这一概念的测试，两个扰乱迁徙的基因被更详细地描述了：大爆炸和Dlg5同源基因CG6509。我们提供的证据表明，Big Bang调节JAK/STAT信号，而Dlg5/CG6509维持簇凝聚力。此外，这些结果表明，通过RNAi靶向一类选定的基因可以发现集体细胞迁移的新调节因子。
Cells often move as collective groups during normal embryonic development and wound healing, although the mechanisms governing this type of migration are poorly understood. The Drosophila melanogaster border cells migrate as a cluster during late oogenesis and serve as a powerful in vivo genetic model for collective cell migration. To discover new genes that participate in border cell migration, 64 out of 66 genes that encode PDZ domain-containing proteins were systematically targeted by in vivo RNAi knockdown. The PDZ domain is one of the largest families of protein-protein interaction domains found in eukaryotes. Proteins that contain PDZ domains participate in a variety of biological processes, including signal transduction and establishment of epithelial apical-basal polarity. Targeting PDZ proteins effectively assesses a larger number of genes via the protein complexes and pathways through which these proteins function. par-6, a known regulator of border cell migration, was a positive hit and thus validated the approach. Knockdown of 14 PDZ domain genes disrupted migration with multiple RNAi lines. The candidate genes have diverse predicted cellular functions and are anticipated to provide new insights into the mechanisms that control border cell movement. As a test of this concept, two genes that disrupted migration were characterized in more detail: big bang and the Dlg5 homolog CG6509. We present evidence that Big bang regulates JAK/STAT signaling, whereas Dlg5/CG6509 maintains cluster cohesion. Moreover, these results demonstrate that targeting a selected class of genes by RNAi can uncover novel regulators of collective cell migration.