RUI: Role of POU factors in the regulation of the timing of metamorphosis

在包括人类在内的许多生物体中，胚后发育的特征是生理学上的突然变化，从而引发生长和形态的巨大变化。虽然参与这些主要的发育转变的神经内分泌变化已经得到很好的表征，这些变化的启动时间的调节仍然知之甚少。POU因子是一种高度保守的转录因子，在脊椎动物青春期参与调节神经内分泌的变化。在甲虫中，去除POU因子，即缺乏侧脉（Vvl），也会导致幼虫经历早熟变态。该项目的目标是研究Vvl如何与已知的变态调节因子相互作用，并研究其他POU因子在变态过程中的作用。为了更好地了解这种蛋白质的作用，该项目将确定基因的调控，蛋白质作用的组织及其基因靶点，在遗传模型系统Tribolium castaneum中使用基因敲除和基因表达分析。在脊椎动物和无脊椎动物中，POU因子似乎在调节胚后发育过渡和性成熟中起着至关重要的作用。因此，该项目具有更广泛的意义，以确定如何POU因子调节基因表达和发育时间在广泛的生物体。重要的是，鉴于目前青年人性早熟发病的趋势，了解发育过渡的调节将具有重要的医学和公共卫生意义。这项拟议中的研究的大部分将涉及来自韦尔斯利学院的女本科生，这是一个来自各种社会经济背景的多元化群体。此外，该项目的一部分将被带入课堂，学生可以进行独立的项目，以学习现代分子技术，最后，在夏季，PI的实验室将接待一些高中生，让来自弱势背景的学生接触科学研究。

In many organisms, including humans, postembryonic development is marked by an abrupt change in physiology that initiates dramatic changes in growth and morphology. While the neuroendocrine changes involved in these major developmental transitions have been well characterized, the regulation underlying the timing of initiation of these changes remains poorly understood. POU factors are highly conserved transcription factors that have been shown to regulate neuroendocrine changes during puberty in vertebrates. In beetles, the removal of the POU factor, Ventral veins lacking (Vvl), also causes larvae to undergo precocious metamorphosis. The goal of the project is to examine how Vvl interacts with the known regulators of metamorphosis and to examine the roles of other POU factors during metamorphosis. To better understand what this protein does, the project will determine the regulation of the gene, the tissues in which the protein acts and its gene targets, using gene knockdown and gene expression analyses in the genetic model system, Tribolium castaneum. In both vertebrates and invertebrates, POU factors appear to play crucial roles in regulating the postembryonic developmental transitions and sexual maturity. Thus, this project has broader implications for identifying how POU factors regulate gene expression and developmental timing in a wide range of organisms. Importantly, given the current trend towards precocious puberty onset among youth, understanding the regulation of developmental transitions will have important medical and public health implications. A majority of the proposed study will involve the female undergraduate students from Wellesley College, a diverse group of people from a wide range of socioeconomic backgrounds. In addition, parts of this project will be brought into the classroom where students can conduct independent projects to learn modern molecular techniques, Finally, during the summers, the PI's lab will host a number of high school students to expose students from disadvantaged backgrounds to scientific research.