Researchers from University of Toronto report details of new studies and findings in the area of retinoblastoma
2007 NOV 19 -- "It has long been known that loss of the retinoblastoma protein (Rb) perturbs neural differentiation, but the underlying mechanism has never been solved. Rb absence impairs cell cycle exit and triggers death of some neurons, so differentiation defects may well be indirect," scientists in Toronto, Canada report. "Indeed, we show that abnormalities in both differentiation and light-evoked electrophysiological responses in Rb-deficient retinal cells are rescued when ectopic division and apoptosis are blocked specifically by deleting E2f transcription factor (E2f) 1. However, comprehensive cell-type analysis of the rescued double-null retina exposed cell-cycle-independent differentiation defects specifically in starburst amacrine cells (SACs), cholinergic interneurons critical in direction selectivity and developmentally important rhythmic bursts. Typically, Rb is thought to block division by repressing E2fs, but to promote differentiation by potentiating tissue-specific factors. Remarkably, however, Rb promotes SAC differentiation by inhibiting E2f3 activity. Two E2f3 isoforms exist, and we find both in the developing retina, although intriguingly they show distinct subcellular distribution. E2f3b is thought to mediate Rb function in quiescent cells. However, in what is to our knowledge the first work to dissect E2f isoform function in vivo we show that Rb promotes SAC differentiation through E2f3a," wrote D. Chen and colleagues, University of Toronto. The researchers concluded: "These data reveal a mechanism through which Rb regulates neural differentiation directly, and, unexpectedly, it involves inhibition of E2f3a, not potentiation of tissue-specific factors." Chen and colleagues published their study in Plos Biology (Rb-mediated neuronal differentiation through cell-cycle-independent regulation of E2f3a. Plos Biology, 2007;5(7):1504-1519). For additional information, contact R. Bremner, University of Toronto, Genetics & Development Division, Toronto Western Research Institute, University of Health Network, Toronto, ON, Canada. The publisher's contact information for the journal Plos Biology is: Public Library Science, 185 Berry St., Ste. 1300, San Francisco, CA 94107, USA. Keywords: Canada, Toronto, Oncology, Ophthalmology, Retinoblastoma, University of Toronto. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.
|
