Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc
Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc
复制标题
DOI：
10.1101/gad.1820009
复制
发表时间：
2009-10-01
影响因子：
10.5
通讯作者：
Mann, Richard S.
中科院分区：
文献类型：
--
作者：
Peng, H. Wayne;Slattery, Matthew;Mann, Richard S.
细胞增殖和存活的精确控制对于动物发育至关重要。Hippo肿瘤抑制途径通过控制转录辅激活因子Yorkie（Yki）的核可用性来调节这两个参数，所述转录辅激活因子Yorkie（Yki）与DNA结合蛋白Scalloped（Sd）一起调节下游靶基因。在这里，我们提供的证据表明，Yki也可以调节靶基因与Homothorax（Hth）和Teashirt（TSH），两个DNA结合转录因子中表达的未定型祖细胞的果蝇眼睛成虫盘。克隆分析表明，Hth和Tsh促进细胞增殖和保护眼祖细胞免于凋亡。遗传上位性实验表明，Hth和Tsh与Yki一起执行这些功能，部分通过上调microRNA bantam。在细胞培养中可以检测到Hth和Yki之间的物理相互作用，我们表明，Hth和Yki结合到一个类似于14 kb的上游的矮脚鸡发夹在眼睛的成虫盘细胞的DNA序列，认为这种调节是直接的。这些数据表明，河马途径使用不同的DNA结合转录因子，这取决于细胞环境。在眼盘中，Hth和Tsh为该通路提供空间信息，促进祖细胞结构域中的细胞增殖和存活。
The accurate control of cell proliferation and survival is critical for animal development. The Hippo tumor suppressor pathway regulates both of these parameters by controlling the nuclear availability of the transcriptional coactivator Yorkie (Yki), which regulates downstream target genes together with Scalloped (Sd), a DNA-binding protein. Here we provide evidence that Yki can also regulate target genes in conjunction with Homothorax (Hth) and Teashirt (Tsh), two DNA-binding transcription factors expressed in the uncommitted progenitor cells of the Drosophila eye imaginal disc. Clonal analyses demonstrate that Hth and Tsh promote cell proliferation and protect eye progenitor cells from apoptosis. Genetic epistasis experiments suggest that Hth and Tsh execute these functions with Yki, in part by up-regulating the microRNA bantam. A physical interaction between Hth and Yki can be detected in cell culture, and we show that Hth and Yki are bound to a DNA sequence similar to 14 kb upstream of the bantam hairpin in eye imaginal disc cells, arguing that this regulation is direct. These data suggest that the Hippo pathway uses different DNA-binding transcription factors depending on the cellular context. In the eye disc, Hth and Tsh provide spatial information to this pathway, promoting cell proliferation and survival in the progenitor domain.