Department of Cell Biology, University of Virginia, Charlottesville, United States.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, Illkirch-Graffenstaden, France.
Elife. 2019 Sep 12;8:e45241. doi: 10.7554/eLife.45241.
In many vertebrates, establishment of Left-Right (LR) asymmetry results from the activity of a ciliated organ functioning as the LR Organizer (LRO). While regulation of the formation of this structure by major signaling pathways has been described, the transcriptional control of LRO formation is poorly understood. Using the zebrafish model, we show that the transcription factors and cofactors mediating or regulating the transcriptional outcome of the Hippo signaling pathway play a pivotal role in controlling the expression of genes essential to the formation of the LRO including ligands and receptors of signaling pathways involved in this process and most genes required for motile ciliogenesis. Moreover, the transcription cofactor, Vgll4l regulates epigenetic programming in LRO progenitors by controlling the expression of writers and readers of DNA methylation marks. Altogether, our study uncovers a novel and essential role for the transcriptional effectors and regulators of the Hippo pathway in establishing LR asymmetry.
在许多脊椎动物中，左右（LR）不对称性的确立是由作为 LR 组织者（LRO）的纤毛器官的活性引起的。虽然已经描述了主要信号通路对该结构形成的调节，但 LRO 形成的转录控制仍知之甚少。使用斑马鱼模型，我们表明，介导或调节 Hippo 信号通路转录结果的转录因子和辅助因子在控制与 LRO 形成相关的基因的表达中起着关键作用，这些基因包括参与该过程的信号通路的配体和受体，以及运动纤毛发生所需的大多数基因。此外，转录共因子 Vgll4l 通过控制 DNA 甲基化标记的写入器和读取器的表达来调节 LRO 祖细胞中的表观遗传编程。总之，我们的研究揭示了 Hippo 通路的转录效应子和调节剂在建立 LR 不对称性方面的新的和重要作用。
