Determination of Cell Fate in the Vertebrate Retina and GFP as a Regulator of Biological Activities

Summary

Date: 
April 23, 2015 - 12:00pm
Location: 
NW B103
About the Speaker
Name: 
Connie Cepko (HMS)

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).

Cepko, CL. Intrinisically different retinal progenitor cells produce specific types of progeny. Nat Rev Neurosci. 2014 Sep;15(9):615-27. doi: 10.1038/nrn3767.

Wang, S., Sengel, C., Emerson, M.M., Cepko, C.L. A gene regulatory network controls the binary fate decision of rod and bipolar cells in the vertebrate retina. Dev Cell. 2014 Aug 20. pii: S1534-5807(14)00484-5. doi: 10.1016

Tang JC, Szikra T, Kozorovitskiy Y, Teixiera M, Sabatini BL, Roska B, Cepko CL. A nanobody-based system using fluorescent proteins as scaffolds for cell-specific gene manipulation. Cell. Aug 15;154(4):928-39. (2013) PMID:23953120