Asymmetric segregation of numb in retinal development and the influence ofthe pigmented epithelium

Asymmetric segregation of cell-fate determinants during cytokinesis plays a n important part in controlling cell-fate choice in invertebrates. During D rosophila neurogenesis, for example, asymmetric segregation of the Numb pro tein, which inhibits Notch signaling, is necessary for the two daughter cel ls of a division to have different fates. In vertebrates, the role of asymm etric segregation of cell-fate determinants is uncertain, and the way the p rocess might be regulated is unknown. We have studied the orientation of ce ll divisions and the distribution of Numb in the developing rat retina. We show that, whereas most retinal neuroepithelial cells divide with their mit otic spindles oriented parallel to the plane of the neuroepithelium, a subs tantial minority divides with their spindles oriented perpendicularly. The proportion of these vertically dividing cells changes during development, p eaking around the day of birth. Numb appears to be inherited only by the ap ical daughter cell when a neuroepithelial cell divides vertically. Similarl y, in dissociated cell cultures, some retinal neuroepithelial cells divide asymmetrically and distribute Numb to only one of the two daughter cells, s uggesting that the dissociated cells can retain their polarity in vitro. Us ing retinal explant cultures, we find that the retinal pigment epithelium a pparently promotes vertical divisions in the neural retina. To our knowledg e, this is the first evidence that asymmetric segregation of cell-fate dete rminants may contribute to cell diversification in the mammalian retina and that an epithelium controls this process by influencing the plane of divis ion in the adjacent neural retina.