转录调控的细胞粘附网络决定了远端末梢细胞的方向性。
Transcriptionally regulated cell adhesion network dictates distal tip cell directionality.
作者信息
Wong Ming-Ching, Kennedy William P, Schwarzbauer Jean E
机构信息
Department of Molecular Biology, Princeton University, Princeton, New Jersey.
出版信息
Dev Dyn. 2014 Aug;243(8):999-1010. doi: 10.1002/dvdy.24146. Epub 2014 May 26.
BACKGROUND
The mechanisms that govern directional changes in cell migration are poorly understood. The migratory paths of two distal tip cells (DTC) determine the U-shape of the C. elegans hermaphroditic gonad. The morphogenesis of this organ provides a model system to identify genes necessary for the DTCs to execute two stereotyped turns.
RESULTS
Using candidate genes for RNAi knockdown in a DTC-specific strain, we identified two transcriptional regulators required for DTC turning: cbp-1, the CBP/p300 transcriptional coactivator homologue, and let-607, a CREBH transcription factor homologue. Further screening of potential target genes uncovered a network of integrin adhesion-related genes that have roles in turning and are dependent on cbp-1 and let-607 for expression. These genes include src-1/Src kinase, tln-1/talin, pat-2/α integrin and nmy-2, a nonmuscle myosin heavy chain.
CONCLUSIONS
Transcriptional regulation by means of cbp-1 and let-607 is crucial for determining directional changes during DTC migration. These regulators coordinate a gene network that is necessary for integrin-mediated adhesion. Overall, these results suggest that directional changes in cell migration rely on the precise gene regulation of adhesion.
背景
细胞迁移方向变化的调控机制尚不清楚。两个远端顶端细胞（DTC）的迁移路径决定了秀丽隐杆线虫雌雄同体性腺的U形。该器官的形态发生提供了一个模型系统，以识别DTC执行两个定型转向所需的基因。
结果
通过在特定DTC菌株中对候选基因进行RNA干扰敲低，我们鉴定出DTC转向所需的两个转录调节因子：cbp-1，CBP/p300转录共激活因子同源物，以及let-607，一种CREBH转录因子同源物。对潜在靶基因的进一步筛选揭示了一个整合素粘附相关基因网络，这些基因在转向中起作用，并依赖于cbp-1和let-607进行表达。这些基因包括src-1/Src激酶、tln-1/踝蛋白、pat-2/α整合素和nmy-2，一种非肌肉肌球蛋白重链。
结论
通过cbp-1和let-607进行的转录调控对于确定DTC迁移过程中的方向变化至关重要。这些调节因子协调一个整合素介导的粘附所必需的基因网络。总体而言，这些结果表明细胞迁移的方向变化依赖于粘附的精确基因调控。
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