Notochord Differentiation in the Ascidian, Ciona Intestinalis

0131758Levine建议的研究重点是描述简单脊索动物--肠囊海鞘--脊索分化的基因调控网络。研究计划包括三个具体目标。首先，蜗牛抑制因子似乎抑制了假定的尾部肌肉中的脊索分化。这将通过使用定义的组织特异性增强剂在电穿孔胚胎中错误表达野生型和突变型蜗牛蛋白来进行测试。第二，短索激活因子的两个不同的靶基因Ezrin和Meg1参与了脊索分化过程中细胞形状的变化。将通过在脊索中表达不同显性-负性形式的蛋白质来研究编码蛋白质的活性。第三条研究路线将探索T盒特异性的基础，即相关的含T转录因子控制不同组织的分化。特别的努力将集中在brachyury和Tbx6上，它们分别调节脊索和尾部肌肉中不同的靶基因集。

0131758LevineThe focus of the proposed study is to characterize the gene regulation networks underlying notochord differentiation in a simple chordate, the ascidian Ciona intestinalis. The research plan includes three specific aims. First, the Snail repressor appears to inhibit notochord differentiation in the presumptive tail muscles. This will be tested by misexpressing both wild-type and mutant forms of the Snail protein in electroporated embryos using defined tissue-specific enhancers. Second, two different target genes of the Brachyury activator, Ezrin and Meg1, have been implicated in mediating cell shape changes during notochord differentiation. The activities of the encoded proteins will be investigated by expressing different dominant-negative forms of the proteins in the notochord. The third line of research will explore the basis of T box specificity, whereby related T-containing transcription factors control the differentiation of distinct tissues. Particular efforts will focus on Brachyury and Tbx6, which regulate distinct sets of target genes in the notochord and tail muscles, respectively.