Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16246-51. doi: 10.1073/pnas.1203045109. Epub 2012 Sep 18.
In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi-treated L4 larvae. We observed expression of 8,000-10,000 genes in the linker cell, 22-25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67-dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.
在后生动物发育和转移性癌症中，迁移细胞必须执行详细、复杂的感应线索、结合基质和移动细胞骨架的程序。秀丽隐杆线虫雄性中的连接细胞经历了一种刻板的迁移，指导性腺器官发生，具有精确的时间，并需要核激素受体 NHR-67。为了更好地理解这是如何发生的，我们对单独分期和解剖的连接细胞进行了 RNA-seq 分析，比较了第三阶段（L3）幼虫、第四阶段（L4）幼虫和 nhr-67-RNAi 处理的 L4 幼虫连接细胞的转录组。我们观察到连接细胞中表达了 8000-10000 个基因，其中 22-25%的基因在 NHR-67 的作用下在发育过程中被上调或下调了 20 倍。在我们通过 RNAi 测试的基因中，22%（204 个中的 45 个）是正常形状和迁移所必需的，这表明许多 NHR-67 依赖性、连接细胞丰富的基因在这种迁移中发挥作用。一类由 NHR-67 上调的意想不到的基因是串联孔钾通道，这是正常连接细胞迁移所必需的。我们还发现了具有人类同源物但没有先前描述的迁移功能的基因的表型。我们的研究结果提供了一个广泛的作用于迁移细胞的基因目录，确定了参与线虫细胞迁移的独特分子功能，并暗示了人类中的类似功能。
