Oxyopia Abstract

March 12, 2004
Friday, Noon
489 Minor Hall

Rod Bremner, PhD
Toronto Western Research Institute, University Health Network, Department of Ophthalmology and Visual Sciences, University of Toronto
Host: John Flannery

Title

"The RB and E2F families in retinal development and cancer"

Abstract

Despite the fundamental role of the Rb gene in retinoblastoma, the effect of its loss on the development of different retinal cell types has never been addressed. Rb-deficient mice die at embryonic day (E) 13-15, thus to study retinal-specific effects we generated a conditional knockout. Previous studies, using either chimeric mice or transgenics expressing proteins that inactivate RB protein function suggested that the common outcome of RB loss is cell death. However, we show that loss of RB or RB plus its relative, p107, has cell specific effects. Three cell types survive RB loss. Our data also pinpoint the time at which RB is most critical for cell cycle regulation in retinal development and suggest a new model for the initiation of retinoblastoma.

RB functions primarily by negatively regulating the E2F family of proteins. E2F1-3, known as the activating E2Fs, are critical for cell division in fibroblasts, and RB binds and suppresses their ability to activate genes required for cell division. We have studied the role of these proteins in retinal development, and their roles in mediating the retinal defects in the RB or RB/p107-deficient retina. Our results challenge the idea that E2F1-3 are indispensable for division in all cell types, and reveal that these E2F family members have highly specific as well as overlapping roles in retinal development and cancer.