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The Journal of Neuroscience, September 19, 2007, 27(38):10143-10152; doi:10.1523/JNEUROSCI.2754-07.2007

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Development/Plasticity/Repair
Interkinetic Nuclear Migration and the Selection of Neurogenic Cell Divisions during Vertebrate Retinogenesis

Lisa M. Baye and Brian A. Link

Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Correspondence should be addressed to Dr. Brian A. Link, Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226. Email: blink{at}mcw.edu

During retinal development, neuroepithelial progenitor cells divide in either a symmetric proliferative mode, in which both daughter cells remain mitotic, or in a neurogenic mode, in which at least one daughter cell exits the cell cycle and differentiates as a neuron. Although the cellular mechanisms of neurogenesis remain unknown, heterogeneity in cell behaviors has been postulated to influence this cell fate. In this study, we analyze interkinetic nuclear migration, the apical–basal movement of nuclei in phase with the cell cycle, and the relationship of this cell behavior to neurogenesis. Using time-lapse imaging in zebrafish, we show that various parameters of interkinetic nuclear migration are significantly heterogeneous among retinal neuroepithelial cells. We provide direct evidence that neurogenic progenitors have greater basal nuclei migrations during the last cell cycle preceding a terminal mitosis. In addition, we show that atypical protein kinase C (aPKC)-mediated cell polarity is essential for the relationship between nuclear position and neurogenesis. Loss of aPKC also resulted in increased proliferative cell divisions and reduced retinal neurogenesis. Our data support a novel model for neurogenesis, in which interkinetic nuclear migration differentially positions nuclei in neuroepithelial cells and therefore influences selection of progenitors for cell cycle exit based on apical–basal polarized signals.

Key words: neurogenesis; cell fate; cell cycle; retina development; neuroepithelia; cell polarity

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Received June 17, 2007; revised July 30, 2007; accepted Aug. 1, 2007.

Correspondence should be addressed to Dr. Brian A. Link, Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226. Email: blink{at}mcw.edu

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