Abstract
Abstract: :
Purpose:The developmental potency of retinal neuroepithelial cells, the progenitors for all retinal cell types, becomes restricted with embryogenesis. Work from many laboratories has indicated that the final retinal cell type fate decision is determined during a critical period that encompasses the last cell cycle and the ensuing post-mitotic cell migration. Interkinetic nuclear migration is the process where the nucleus moves within proliferating neuroepithelial cells in phase with the cell cycle. I have investigated the last nuclear migration before cell cycle withdrawal as a potential cell fate determining mechanism for vertebrate retinal patterning Methods:In vivo time-lapse movies of interkinetic nuclear migrations were made in developing zebrafish embryos. Nuclei were labeled by transgenesis with DNA encoding histoneH2B-GFP fusion protein. Inhibitors of specific stages of the cell cycle were then used to transiently block nuclear migration and retinal cell type patterning was assessed using cell type specific markers. Results:In untreated embryos, heterogeneity among retinal neuroepithelial cells was observed with respect to nuclear migration. The kinetics of nuclear migration was not significantly different between cells, however the apical to basal distance traversed by the nuclei did vary. In addition, neuroepithelial cells showed differential pausing (durations and frequency) in G1/S-phase. Importantly, transient inhibition of the cell cycle resulted in patterning defects within the differentiated retina. Conclusion:These data are consistent with a role for interkinetic nuclear migration in retinal cell fate specification and/or patterning. Potential mechanisms will be discussed.
Keywords: 564 retinal development • 316 animal model • 340 cell-cell communication