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.
