Mechanism of an Evolutionary Change in Development

这个项目的目的是了解脊索动物身体计划进化变化的机制。 对于这些研究，PI开发了一个模型系统，由两种具有不同幼虫的密切相关的海鞘物种组成。 海鞘蝌蚪幼虫具有脊索动物的所有特征，但只包含2500个细胞和6种不同的组织。 Molgula oculata（有尾种）有一个游泳的蝌蚪幼虫，尾巴含有脊索和横纹肌细胞，而Molgula occulta（无尾种）有一个不动的幼虫，缺乏这些特征。 无尾物种的卵子与有尾物种的精子受精后，杂交幼虫的脊索和尾巴得以恢复，这表明它们部分是由于合子尾形成基因的变化而丢失的。 在以前的资助期间，PI已经确定了一些尾巴形成基因。 该项目扩展了这些研究，集中在马恩岛和山猫基因，这分别编码一个假定的转录因子和RNA解旋酶。 初步研究表明，在有尾物种的基因组中，马恩岛和山猫存在于一个类似操纵子的簇中。 在这里，PI建议确定这些相关基因如何调节海鞘的进化和发育。 首先，PI将表征整个马恩岛/山猫基因复合体，以确定是否存在其他尾形成基因，以及这些基因是否确实是有尾物种中操纵子的一部分。 第二，PI将决定Manx和山猫基因在尾部发育中的作用，特别是在介导细胞增殖和程序性细胞死亡中的作用。 第三，PI将表征无尾物种中的Manx/山猫基因，以确定可能积累了哪些突变导致尾退化。 最后，PI将研究Manx和山猫以及forkhead和Brachyury（T）基因之间的潜在相互作用，这些基因已知参与海鞘的轴和脊索发育。 因此，通过研究海鞘幼虫的尾巴形成基因，PI希望阐明进化过程中脊索动物身体计划起源的机制。

The purpose of this project is to understand the mechanisms underlying evolutionary changes in the chordate body plan. For these studies, the PI has developed a model system consisting of two closely-related ascidian species with different larvae. The ascidian tadpole larva exhibits all the hallmarks of a chordate yet contains only 2500 cells and six different tissues. Molgula oculata (the tailed species) has a swimming tadpole larva with a tail containing a notochord and striated muscle cells, whereas Molgula occulta (the tailless species) has an immotile larva lacking these features. Fertilization of tailless species' eggs with tailed species' sperm results in restoration of the notochord and tail in the hybrid larvae, suggesting that they were lost in part by changes in zygotic tail-forming genes. In previous funding periods the PI has identified some of the tail forming genes. This project extends those studies in focusing on the Manx and bobcat genes, which encode a putative transcription factor and an RNA helicase respectively. Preliminary studies show that Manx and bobcat are present in an operon-like cluster in the tailed species' genome. Here the PI proposes to determine how these linked genes regulate ascidian evolution and development. First, the PI will characterize the entire Manx/bobcat gene complex to determine whether other tail-forming genes are present and whether these genes are indeed part of an operon in the tailed species. Second, the PI will determine the roles of the Manx and bobcat genes in tail development, particularly in mediating cell proliferation and programmed cell death. Third, the PI will characterize the Manx/bobcat genes in the tailless species to determine what mutations may have accumulated to result in tail regression. Finally, the PI will study the potential interactions between Manx and bobcat and the forkhead and Brachyury (T) genes, which are known to be involved in axis and notochord development in ascidians. Thus, by studying tail forming genes in ascidian larvae, the PI hopes to shed light on the mechanisms underlying the origin of the chordate body plan during evolution.