Publication
Numb is required for the production of terminal asymmetric cell divisions in the developing mouse retina
Publisher:
Society for Neuroscience
Date:
28-11-2012
DOI:
10.1523/JNEUROSCI.4127-12.2012
Abstract: In the developing nervous system, cell ersification depends on the ability of neural progenitor cells to ide asymmetrically to generate daughter cells that acquire different identities. While much work has recently focused on the mechanisms controlling self-renewing asymmetric isions producing a differentiating daughter and a progenitor, little is known about mechanisms regulating how distinct differentiating cell types are produced at terminal isions. Here we study the role of the endocytic adaptor protein Numb in the developing mouse retina. Using clonal numb inactivation in retinal progenitor cells (RPCs), we show that Numb is required for normal cell-cycle progression at early stages, but is dispensable for the production of self-renewing asymmetric cell isions. At late stages, however, Numb is no longer required for cell-cycle progression, but is critical for the production of terminal asymmetric cell isions. In the absence of Numb, asymmetric terminal isions that generate a photoreceptor and a non-photoreceptor cell are decreased in favor of symmetric terminal isions generating two photoreceptors. Using live imaging in retinal explants, we show that a Numb fusion protein is asymmetrically inherited by the daughter cells of some late RPC isions. Together with our finding that Numb antagonizes Notch signaling in late-stage RPCs, and that blocking Notch signaling in late RPCs almost completely abolishes the generation of terminal asymmetric isions, these results suggest a model in which asymmetric inheritance of Numb in sister cells of terminal isions might create unequal Notch activity, which in turn drives the production of terminal asymmetric isions.