IOS-0745782 Morphogenesis of the Vertebrate Eye
While eye formation is a well-conserved process across animals, the molecular mechanisms and the cell and tissue movements that facilitate many aspects of the process remain unclear. Research in this CAREER award focuses on understanding the molecular and cellular underpinnings of vertebrate eye development. Of particular interest to the Gross lab are the mechanisms that lead to the formation of the ventral optic cup, which subsequently undergoes a number of distinct cellular movements that are required for normal eye formation. To identify these mechanisms and genetic components required for ventral optic cup formation, the Gross lab utilizes the zebrafish embryo as a model system in which genetic, molecular and in vivo imaging techniques can be applied. The research addresses two central questions in eye development: (1) What are the regulatory components that lead to ventral optic cup formation, and how do these components interact as a network to facilitate this process? and (2) What are the cellular mechanisms that govern optic cup morphogenesis, and how are these regulated?
The Intellectual Merit of this project lies in a betterment of the understanding of the molecular and developmental mechanisms underlying eye formation, processes that have not been well characterized in any organism. The Broader Impacts of the project are threefold: (1) numerous training opportunities are provided for graduate, undergraduate and high school students in contemporary molecular and genetic techniques; (2) the research is integrated into a cutting edge laboratory course for undergraduate students that involves them first-hand in the research process and enables them to gain a unique research experience as part of their undergraduate training; and (3) the PI, graduate and undergraduate students participate in a number of outreach programs designed to attract and retain underrepresented students in the sciences, and to provide meaningful research experiences to these students.
The long-term goal of our research is to define the morphogenetic, cell biological and molecular events underlying eye formation. Research funded in this grant focused in several distinct aspects of eye development using the zebrafish embryo as a model system, and our work has resulted in several advances. 1) We have identified a regulatory pathway that operates in the ventral region of the optic cup (the tissue that generates the eye), and this pathway functions to maintain cell survival and enable the optic cup to form properly. 2) We have identified two mutations that compromise growth of the eye and its pigmentation. These two mutations function in the biochemical pathway that leads to the formation of ATP and GTP; interestingly, one pathway (the ATP pathway) stimulates eye growth, while the other (the GTP pathway) stimulates pigmentation. 3) We identified a mutation in a gene, hps5, that is required for the formation of pigment in the eye and we identified a potential mechanism by which it acts to stabilize other components required for formation of the pigment containing organelles in the eye (melanosomes). 4) We defined the cell biological underpinnings of optic cup morphogenesis, and specifically, we identified a regulatory pathway that functions in a distinct region of the ventral optic cup called the optic fissure to facilitate closure of the optic cup during early eye development. Research funded in this grant provided training opportunities for graduate, undergraduate and high school students, and training of a postdoctoral fellow. Our research was also integrated into several undergraduate courses, and was presented at a variety of outreach events at our university.
