17-P035 Functional heterogeneity of murine embryonic stem cells revealed through translational amplification in an early endoderm marker

neural stem, we are using Xenopus retina as a model system. Our expression analyses revealed that both Msi1 and Msi2 are expressed in retinal stem cells. In order to highlight the function of Msi genes, we ectopically expressed Msi1 and Msi2 by mRNA injection. We found that Msi misexpression promotes the formation of epidermal protrusions, reminiscent of skin tumors and strongly expressing the stem cell marker XHes1 and CyclinD1. In the retina, overexpression of both Msi genes enhances cell cycle kinetics. In addition, we observed a decreased expression of the cell cycle inhibitor p27-Xic1, suggesting that Msi might also inhibit cell cycle exit of retinal precursors. Finally, preliminary coimmunoprecipitation experiments suggest that Msi1 and Msi2 form heterodimers. Altogether, our data suggest that Msi RNA-binding proteins could be involved in the modulation of retinal stem cell/precursor proliferation and that their misregulation could lead to tumor formation. Loss of function analyses are under way to support our model. Furthermore, to investigate Msi gene regulation by signaling pathways involved in the maintenance of retinal stem cells, we are currently evaluating their expression following pharmacological perturbation of Notch, Hedgehog and Wnt pathways.