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L.M. Baye, B.A. Link; Interkinetic Nuclear Migration and Cell Cycle Exit in Zebrafish Retinal Neuroepithelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4176.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative neuroepithelial cells, including those of the retina, undergo interkinetic nuclear migration (IKNM). This cellular behavior is characterized by the apical–basal oscillations of the nucleus in phase with stages of the cell cycle. At the onset of retinogenesis, cell cycle exit of neuroepithelial cells is coordinated spatially and temporally in successive waves. However, within any wave, only a subset of neuroepithelial cells leave the mitotic cycle. To explore the cellular basis of this phenomenon, we have examined heterogeneity in parameters of IKNM and tested whether aspects of this cell behavior correlate with mitotic withdrawal.
Confocal time–lapse imaging in live zebrafish embryos was used to characterize IKNM within retinal neuroepithelial progenitor cells. Cell transplantation was performed to generate small, isolated cell clones for imaging that possessed fluorescently labeled nuclei and a transgene that would be expressed when a cell became post–mitotic. We investigated three parameters of IKNM: cell cycle period, maximum basal position, and the time the nuclei resided at the most basal position.
We first found that there is significant heterogeneity in the three parameters of IKNM examined – cell cycle period, maximal basal position, and time at the most basal position. This heterogeneity can be seen both within family lineages and between unrelated clones. Importantly, we found correlations between two of these parameters and the decision of the cell to exit the cell cycle. Specifically, cells that became post–mitotic had a statistically shorter cell cycle and nuclei that traveled a greater distance basally were significantly more likely to exit the cell cycle. No cells with nuclei that traveled less than 29% of the neuroepithelium exited the cell cycle.
We have characterized IKNM in retinal neuroepithelial cells and found significant heterogeneity in the three parameters examined. Analysis revealed heterogeneity between both clonally related and unrelated cells. Using a transgene that marked cell cycle exit, we found that both the cell cycle period and nuclear migration distance correlates with cell cycle withdrawal. Progenitor cells with short cell cycle periods and nuclei that travel greater basal distances are biased to produce daughter cells that become post–mitotic. This data is consistent with IKNM functioning as a selection criterion for retinal progenitor cell cycle exit. Specific models for how the position of the nucleus regulates cell cycle exit will be discussed.
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