MYC proteins promote neuronal differentiation by controlling the mode of progenitor cell division

Synopsis image This study reveals an unexpected role for MYC in the control of stemness versus differentiation of neural stem cells in vivo and shows that Myc represses Notch signaling and promotes asymmetric neurogenic cell divisions. Elevated MYC levels increase neurogenesis in the developing chick neural tube The neurogenic function of MYC depends on the integrity of the polarized neural tissue MYC promotes apico-basal neurogenic divisions Abstract The role of MYC proteins in somatic stem and progenitor cells during development is poorly understood. We have taken advantage of a chick in vivo model to examine their role in progenitor cells of the developing neural tube. Our results show that depletion of endogenous MYC in radial glial precursors (RGPs) is incompatible with differentiation and conversely, that overexpression of MYC induces neurogenesis independently of premature or upregulated expression of proneural gene programs. Unexpectedly, the neurogenic function of MYC depends on the integrity of the polarized neural tissue, in contrast to the situation in dissociated RGPs where MYC is mitogenic. Within the polarized RGPs of the neural tube, MYC drives differentiation by inhibiting Notch signaling and by increasing neurogenic cell division, eventually resulting in a depletion of progenitor cells. These results reveal an unexpected role of MYC in the control of stemness versus differentiation of neural stem cells in vivo.