Determination of cell fate in the vertebrate retina
Constance Cepko, PhD
Professor of Genetics, Harvard Medical SchoolInvestigator, Howard Hughes Medical Institute
Host: Thomas Südhof
The complexity of the cellular composition of the central nervous system presents a fascinating problem for developmental biologists. One approach to unraveling the mechanisms that generate such complexity is to determine the progenitor-progeny, or lineage, relationships. Such studies have been conducted in various areas of the CNS, with some of the initial studies using retroviral vectors to mark clones in the retina. These studies established that retinal progenitor cells (RPCs) are multipotent, capable of giving rise to more than one cell type. They also showed that the number and type of cells that derived from individual RPCs were highly variable. This raised the question of whether the variability was due to intrinsic differences among RPCs or to extrinsic and/or stochastic effects on equivalent RPCs or their progeny. Newer lineage studies have demonstrated some intrinsic aspects, in that terminally dividing RPCs can make specific pairs of daughter cells, with the specificity extending to very specific subtypes of retinal neurons (Cepko, 2014). In addition to these lineage studies, the talk will cover the recent elucidation of a gene regulatory network that governs a binary fate decision in the retina. These studies used electroporation of Crispr/Cas to effect genetic modifications in the mouse retina (Wang et al. 2014). Finally, the development of GFP as a scaffold to allow the manipulation of gene expression only in GFP+ cells will be described (Tang et al. 2013).
Dr. Cepko is the Bullard Professor of Genetics and Neuroscience at Harvard Medical School and an Investigator of the Howard Hughes Medical Institute. She received her PhD degree from the Massachusetts Institute of Technology, working with Phillip Sharp, and remained at MIT as a postdoctoral fellow in the laboratory of Richard Mulligan, where she was involved in the development of retrovirus-mediated gene transduction. Her current research is focused on the development of the central nervous system, with an emphasis on the retina. Her laboratory has also been working to develop gene therapy for prolonging vision in genetic forms of blindness, and in developing viral vectors for tracing neuronal circuitry.