Gap Junctions Mediate Bystander Cell Death in Developing Retina
Open Access
- 23 July 2003
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 23 (16) , 6413-6422
- https://doi.org/10.1523/jneurosci.23-16-06413.2003
Abstract
During development of the retina, programmed cell death helps to establish the final size and distribution of various cell classes in distinct layers of the tissue. Here we show that dying cells in the developing ganglion and inner nuclear layers are clustered spatially and that gap junction inhibitors decrease the clustering of dying cells. To confirm the role of gap junctions in cell death, we induced targeted cell death via intracellular cytochromec(Cc) and examined the induced cells and their neighbors for apoptotic morphology or caspase-3 cleavage. These studies indicate that bystander killing extends to coupled cells.Quantitative studies of bystander killing were performed by scrape-loading retinas with Ccin the presence of rhodamine dextran (RD; to identify Cc-loaded cells) and by counting pyknotic cells in cryosections. Although only 1.5% of control scrape-loaded cells (RD alone) showed apoptotic morphology, 97% of Ccscrape-loaded cells were pyknotic. Moreover, bystander killing extended to neighboring cells, not labeled with RD, and was reduced significantly by the gap junction inhibitors octanol and carbenoxolone. We hypothesize that dying cells in the retina generate a gap junction-permeant apoptotic signal that mediates bystander killing. This novel finding of naturally occurring bystander cell death may have important implications in the histogenesis and pathology of the nervous system.Keywords
This publication has 49 references indexed in Scilit:
- The anti-death league: associative control of apoptosis in developing retinal tissueBrain Research Reviews, 2000
- Rods and cones project to the inner plexiform layer during developmentJournal of Comparative Neurology, 1999
- Apoptosis induced by microinjection of cytochrome c is caspase-dependent and is inhibited by Bcl-2Cell Death & Differentiation, 1998
- Developmental neuronal death is not a universal phenomenon among cell types in the chick embryo retinaJournal of Comparative Neurology, 1998
- Nitric Oxide Reversibly Inhibits Seven Members of the Caspase Family via S-NitrosylationBiochemical and Biophysical Research Communications, 1997
- Quantification of Normal Cell Death in the Rat Retina: Implications for Clone Composition in Cell Lineage AnalysisEuropean Journal of Neuroscience, 1995
- Cellular degeneration and synaptogenesis in the developing retina of the ratJournal of Comparative Neurology, 1987
- Electrophysiological properties of gap junctions between dissociated pairs of rat hepatocytes.The Journal of cell biology, 1986
- Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activitiesCellular and Molecular Life Sciences, 1978
- CELL DEATHS IN NORMAL VERTEBRATE ONTOGENYBiological Reviews, 1951