CAREER: Direct target genes of Zic1 in research and education

职业：Zic1 在研究和教育中的直接靶基因

• 批准号: 0846168
• 负责人: Christa Merzdorf
• 金额: $ 76.57万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0846168&HistoricalAwards=false
• 关键词: CAREER; Direct; target; genes; Zic1

During early embryonic development, the expression of large numbers of genes must be precisely orchestrated to allow correct morphogenesis of an organism. Thus, studying gene regulatory networks is crucial to understanding the molecular mechanisms that govern early neural development. The Zic1 transcription factor plays multiple and critical roles in early neural development, for example when neural tissue is first set aside and later during formation of the cerebellum. Despite its critical roles in regulating genes during early neural development, little is known about the molecular pathways that are regulated by this transcription factor. A screen conducted in the PI's laboratory was designed to identify genes that are directly regulated by Zic1. Four of these genes are the focus of the proposed studies. The first is an aquaglyceroporin (aqp-3b), which is specifically expressed in the neural folds. It is expected to be involved in closure of the neural tube. Three additional genes (cpl-1, CRABP-II, and SRC-3) promote retinoic acid signaling, which plays critical roles in hindbrain development. The experiments in this project aim to identify a mechanism through which Zic1 regulates neural tube closure and may show that Zic1 is a previously unknown modulator of retinoic acid signaling. Together, the data from these experiments will significantly enhance our understanding of the molecular mechanisms through which the transcription factor Zic1 regulates early neural development. The objectives of the educational activities are to integrate research and teaching by developing a research-based course that introduces a larger group of students to hands-on research than is possible in an individual research laboratory and will allow development of lasting skills in independent inquiry-based thinking. The undergraduates will examine additional direct target genes of the Zic1 transcription factor. The resulting projects will be continued inside the classroom in subsequent years of the course, and outside the classroom by undergraduate students in independent research projects within the PI's laboratory. Thus, the course will help attract talented undergraduate students into the laboratory, who might previously not have considered research an option. Further, outreach activities to middle schools and tribal colleges will provide teaching opportunities for undergraduate students that will foster a deeper understanding of their own work and contribute to BRIDGES, a program that facilitates the transition of Native American students from tribal colleges to four-year institutions.

在早期胚胎发育期间，大量基因的表达必须经过精确的协调，才能使有机体正确的形态发生。因此，研究基因调控网络对于理解支配早期神经发育的分子机制至关重要。Zic1转录因子在早期神经发育中发挥着多种关键作用，例如，当神经组织最初被搁置时，以及后来在小脑形成期间。尽管它在早期神经发育过程中对基因的调控起着关键作用，但人们对这种转录因子调控的分子途径知之甚少。在PI的实验室中进行的一种筛查旨在识别由Zic1直接调控的基因。这些基因中的四个是拟议研究的重点。第一种是水甘油孔蛋白(AQP-3b)，它在神经皱折中特异表达。预计它将参与神经管的关闭。另外三个基因(Cpl-1、CRABP-II和SRC-3)促进维甲酸信号传递，维甲酸在后脑发育中发挥关键作用。本项目中的实验旨在确定Zic1调节神经管关闭的机制，并可能表明Zic1是一个先前未知的维甲酸信号调节器。总之，这些实验的数据将极大地增强我们对转录因子Zic1调节早期神经发育的分子机制的理解。教育活动的目标是通过开发一门以研究为基础的课程，将研究和教学结合起来，使更多的学生接触到实践研究，而不是在单个研究实验室中，并将允许发展基于独立探究的思维的持久技能。本科生将研究Zic1转录因子的其他直接靶基因。由此产生的项目将在课程的后续几年继续在课堂内进行，并由本科生在PI实验室内的独立研究项目中继续在课堂外进行。因此，这门课程将有助于吸引有才华的本科生进入实验室，他们以前可能不会考虑进行研究。此外，面向中学和部落大学的外展活动将为本科生提供教学机会，帮助他们更深入地了解自己的工作，并为桥梁做出贡献，这是一个促进美国原住民学生从部落大学过渡到四年制院校的项目。