CAREER: A Cellular and Molecular Analysis of a Specific Retinal Lineage that Generates Cone Photoreceptors and Horizontal Cells

Cuny City College, New York NY

Investigators

Abstract

An embryo develops from a single cell and this cell generates new cells with increasingly specific functions. For each tissue, there are progenitor cells that then generate more new cells that make up that tissue. Cells that allow us to see color, cone photoreceptors, are formed from progenitor cells in the developing eye. This project will focus on how the progenitor cells form these photoreceptors. The information that directs this process is found in DNA. Experiments will use specific DNA sequences that are involved in the formation of cone photoreceptors to track the progenitor cells in real time as they change into new cells that become cone photoreceptors. This research is expected to lead to new insights into how unique cells are formed during eye development. In addition, this project will engage early stage undergraduates to participate in both this research project and to be leaders of an outreach activity to the New York Public School system. Middle school students will be introduced to what it is to be a scientist, which will open the door to the possibility that they can also become one. This CAREER award will allow the Principal Investigator to develop a sustainable integrated research and outreach program at a large minority serving institution in Harlem. It has recently been recognized that there are retinal progenitor cell populations that are restricted in the cell types that they will generate. The goal of this study is to investigate one of these populations that preferentially generates cone photoreceptors and horizontal cells. To accomplish this, multiple approaches that use cell-type specific transcriptional regulatory elements will be applied. At the cellular level, these elements will be used to determine the subtypes of cone and horizontal cells formed from these progenitor cells. In addition, live imaging will be used to analyze the daughter fates of single cone/horizontal cell progenitors to define the heterogeneity of the lineage. At the molecular level, the role of the Notch-Delta signaling pathway in this progenitor lineage will be examined. Finally, whole transcriptome and epigenome signatures of cells as they transition through the cone/horizontal cell progenitor lineage will be determined. At its conclusion, this project is expected to provide a novel molecular examination of a genetically defined retinal lineage.