Cellular/Molecular
Death by Association
Gap Junctions Mediate Bystander Cell Death in Developing Retina
Karen Cusato, Alejandra Bosco, Renato Rozental, Cinthya A. Guimaraes, Benjamin E. Reese, Rafael Linden, and David C. Spray
(see pages 6413-6422)
Cell death normally occurs during neuronal development, involving cell-specific signals that initiate apoptosis. In this issue, Cusato et al. address an interesting aspect of cell death, the observation that dying cells can be clustered. They examined the possibility that gap junctions allow passage of toxic metabolites or signals via these intercellular channels, thus causing “bystander killing.” They found that dying cells (as detected by cell morphology or TUNEL staining) in developing rat retina were often clustered. Because apoptotic cells are cleared rapidly (in ∼1 hr), the clustering suggests synchronized death. Treatment with a gap junction blocker reduced the clustering of dying cells. They then “scrape” loaded a proportion of cells in the isolated retina with cytochrome c (Cc), normally released from mitochondria during apoptosis and a trigger for caspases that lead to apoptosis. Because Cc is too large to pass through gap junctions, it should only activate caspases in loaded cells. Yet, caspase activation was also seen in bystander cells. Blocking of gap junctions “rescued” the bystander cells but not cells that had been directly loaded with Cc. The authors suggest that gap junctions play an important role in bystander cell death, although the putative gap-junction-permeable mediator of this effect remains unknown.
Development/Plasticity/Repair
Making the Olfactory Bulb Attractive
The left panel diagrams cell migration from the forebrain to the OB. The right panel shows migrating cells labeled by the lipophilic dye DiI. See Liu et al for details.
Neuronal Migration from the Forebrain to the Olfactory Bulb Requires a New Attractant Persistent in the Olfactory Bulb
Guofa Liu and Yi Rao
(see pages 6651-6659)
GABAergic interneurons in the olfactory bulb (OB) are continuously generated throughout life. Their precursors migrate from the subventricular zone (SVZ) to the OB along the rostral migratory pathway, a distance of several centimeters in primates. The SVZ is known to secrete a repellant molecule that may help drive migrating cells from the zone, but how they find their way to the OB remains in question. Liu and Rao now suggest that the migrating neuronal precursors can follow their own noses to the OB. Based on bio-assays in explants, the authors report that migrating cells sense a diffusible attractant that originates in the glomerular layer of the OB. Migration could not be induced by known chemoattractants, suggesting the presence of a novel attractant molecule. Although the molecule was not identified, the results suggest that this striking neuronal migration involves both a push and a pull.
Behavioral/Systems/Cognitive
STOP and GO in the Superior Colliculus
Controlled Movement Processing: Superior Colliculus Activity Associated with Countermanded Saccades
Martin Paré and Doug P. Hanes
(see pages 6480-6489)
Control of movement necessarily involves not only signals that initiate and execute the movement but also signals that can cancel or withhold a commanded movement. Such stopping behavior has been studied using a “countermanding” paradigm: basically a test of the ability to STOP once a GO stimulus has been presented. This race between GO and STOP signals can provide a glimpse of the underlying temporal dynamics, with stopping becoming increasingly difficult as the delay increases after a GO signal. Saccades, the rapid eye movements that realign our visual axis, are a good model system for examining such STOP and GO signaling. Previous studies have suggested that neurons in the frontal eye fields control saccade cancellation, and that superior colliculus (SC) neurons in the brainstem are necessary for saccade production. In this week's Journal, Paré and Hanes adapted the countermanding paradigm to examine the saccade-related and fixation-related neurons of the primate SC. The discharge pattern of SC neurons was consistent with involvement in both execution and cancellation of saccadic movements. These results suggest that the SC is involved in the control rather than just in the execution of saccadic eye movements.
