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The Journal of Neuroscience, August 1, 2001, 21(15):5643-5651

Asymmetric Segregation of Numb in Retinal Development and the Influence of the Pigmented Epithelium

Michel Cayouette1, Alan V. Whitmore1, Glen Jeffery2, and Martin Raff1

1 Medical Research Council Laboratory for Molecular Cell Biology and the Biology Department, University College London, London WC1E 6BT, United Kingdom, and 2 Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom

Asymmetric segregation of cell-fate determinants during cytokinesis plays an important part in controlling cell-fate choice in invertebrates. During Drosophila neurogenesis, for example, asymmetric segregation of the Numb protein, which inhibits Notch signaling, is necessary for the two daughter cells of a division to have different fates. In vertebrates, the role of asymmetric segregation of cell-fate determinants is uncertain, and the way the process might be regulated is unknown. We have studied the orientation of cell divisions and the distribution of Numb in the developing rat retina. We show that, whereas most retinal neuroepithelial cells divide with their mitotic spindles oriented parallel to the plane of the neuroepithelium, a substantial minority divides with their spindles oriented perpendicularly. The proportion of these vertically dividing cells changes during development, peaking around the day of birth. Numb appears to be inherited only by the apical daughter cell when a neuroepithelial cell divides vertically. Similarly, in dissociated cell cultures, some retinal neuroepithelial cells divide asymmetrically and distribute Numb to only one of the two daughter cells, suggesting that the dissociated cells can retain their polarity in vitro. Using retinal explant cultures, we find that the retinal pigment epithelium apparently promotes vertical divisions in the neural retina. To our knowledge, this is the first evidence that asymmetric segregation of cell-fate determinants may contribute to cell diversification in the mammalian retina and that an epithelium controls this process by influencing the plane of division in the adjacent neural retina.

Key words: retina; CNS; development; neuroepithelial cells; Numb; asymmetric division; mitotic spindle


Copyright © 2001 Society for Neuroscience  0270-6474/01/21155643-09$05.00/0


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