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，胚胎后发育的特点是生理上的突然变化，从而引发生长和形态上的戏剧性变化。虽然这些重大发育转变中涉及的神经内分泌变化已经有了很好的特征，但这些变化的启动时机背后的调控仍然知之甚少。POU因子是高度保守的转录因子，已被证明调节脊椎动物青春期神经内分泌的变化。在甲虫中，去除POU因子，即腹侧静脉缺乏(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功能，该项目将利用基因敲除和基因表达分析来确定该基因的调控，该蛋白质在其中发挥作用的组织及其基因靶标在遗传模型系统--卡氏拟谷盗中进行。在脊椎动物和无脊椎动物中，POU因子似乎在调节胚胎后发育过渡和性成熟方面发挥着关键作用。因此，该项目对于确定POU因子如何在广泛的生物体中调节基因表达和发育时机具有更广泛的意义。重要的是，鉴于目前青春期早熟的趋势，了解发育转变的调节将具有重要的医学和公共卫生意义。这项拟议中的大部分研究将涉及卫尔斯理学院的女本科生，这是一个来自广泛社会经济背景的不同群体。此外，这个项目的一部分将被带入教室，学生可以在那里进行独立的项目来学习现代分子技术，最后，在暑假期间，PI的实验室将接待一些高中生，让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.