CAREER: Direct target genes of Zic1 in research and education

在早期胚胎发育期间，大量基因的表达必须精确地协调以允许有机体的正确形态发生。 因此，研究基因调控网络对于理解控制早期神经发育的分子机制至关重要。 Zic 1转录因子在早期神经发育中起着多重和关键的作用，例如当神经组织首先被搁置时，以及后来在小脑形成期间。 尽管它在早期神经发育过程中调控基因的关键作用，但对这种转录因子调控的分子途径知之甚少。 在PI实验室进行的筛选旨在鉴定由Zic 1直接调控的基因。 其中四个基因是拟议研究的重点。 第一种是水甘油孔蛋白（aqp-3b），它在神经褶皱中特异性表达。 预计它将参与神经管的闭合。 另外三个基因（cpl-1，CRABP-II和SRC-3）促进视黄酸信号传导，这在后脑发育中起着关键作用。 该项目中的实验旨在确定Zic 1调节神经管闭合的机制，并可能表明Zic 1是一种以前未知的视黄酸信号调节剂。 总之，来自这些实验的数据将显著增强我们对转录因子Zic 1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个研究型课程，将研究和教学结合起来，该课程向更多的学生介绍了比在单个研究实验室中可能进行的动手研究，并将允许发展独立探究式思维的持久技能。 本科生将研究Zic 1转录因子的其他直接靶基因。 由此产生的项目将在随后几年的课程中继续在课堂内进行，并在PI实验室内的独立研究项目中由本科生在课堂外进行。 因此，该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研究。 此外，对中学和部落学院的外联活动将为本科生提供教学机会，这将促进对自己工作的更深入了解，并为桥梁做出贡献，这是一个促进美洲原住民学生从部落学院过渡到四年制大学的计划。

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.