| Abstract No.: | B-A2014 |
| Country: | Canada |
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| Title: | NUMB PROMOTES BOTH PROGENITOR AND NEURONAL CELL FATES AT DISTINCT STAGES OF RETINAL DEVELOPMENT |
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| Authors/Affiliations: | 1 Amel Kechad*; 1 Michel Cayouette;
1 IRCM, Montreal, QC
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| Content: | Objectives: The production of cell diversity in multicellular organisms depends on asymmetric cell divisions, in which the mother cell segregates cell fate determinants asymmetrically into only one of the two daughter cells, thereby instructing different fates. In the developing retina, the cell fate determinant Numb, a Notch signalling inhibitor, is asymmetrically localized in mitotic retinal progenitor cells and, depending on the orientation of cell division, inherited symmetrically or asymmetrically by the daughter cells. The precise role of Numb in vertebrate neural cell fate decisions, however, remains unclear. Conditional inactivation of Numb in the developing mouse cortex suggests that Numb specifies the progenitor cell fate, but since Numb was inactivated from early stages of corticogenesis (E8.5-E10.5), the specific role of Numb at later stages remains unknown.
Methods and Results: Here we used the mouse retina as a model system to study Numb function at different stages of neural development. We first used the Cre-loxP system to direct restricted in vivo inactivation of Numb in the retina from E10.5. Analysis of adult mutant retinas showed reduced neuronal differentiation, whereas analysis of embryonic mutant retinas showed reduced proliferation. It remained unclear, however, whether reduced neuronal differentiation was indirectly due to decreased proliferation at early stages or whether Numb directly controls neuronal differentiation at late stages. To test this model, we used retroviral vectors expressing Cre recombinase and GFP to infect NumbloxP/loxP mouse retinas at early and late stages of retinal development. Analysis of cell composition and size of each resulting knockout clone showed that early inactivation of Numb significantly reduces clone size, whereas late inactivation of Numb does not affect clone size but drastically decrease non-photoreceptor cell production.
Conclusion: These results indicate that Numb promotes the progenitor fate at early stages of development, whereas it promotes the non-photoreceptor cell fate at later stages, suggesting a model in which Numb regulates different types of asymmetric cell divisions (Progenitor + Neuron or Neuron A + Neuron B) at distinct stages of development.
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