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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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