title: MYC proteins promote neuronal differentiation by controlling the mode of progenitor cell division.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC) Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Zinin
authors.forename: Igor
authors.initials: I
authors.lastname: Adameyko
authors.forename: Margareta
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fritz
authors.forename: Per
authors.initials: P
authors.lastname: Uhlén
authors.forename: Patrik
authors.initials: P
authors.lastname: Ernfors
authors.forename: Marie Arsenian
authors.initials: MA
authors.lastname: Henriksson
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D063928:Ependymoglial Cells / Q000502:physiology; D015870:Gene Expression; D058953:Neural Stem Cells / Q000502:physiology*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology; D055495:Neurogenesis; D016274:Oncogene Protein p55(v-myc) / Q000502:physiology*; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D030161:Avian Proteins; D016274:Oncogene Protein p55(v-myc); D016271:Proto-Oncogene Proteins c-myc; D051880:Receptors, Notch