Cortical neurogenesis requires Bcl6-mediated transcriptional repression of multiple self-renewal-promoting extrinsic pathways.
journal contributionposted on 2020-01-09, 16:44 authored by Jerome Bonnefont, Luca Tiberi, Jelle van den Ameele, Delphine Potier, Zachary B Gaber, Xionghui Lin, Angéline Bilheu, Adèle Herpoel, Fausto D Velez Bravo, François Guillemot, Stein Aerts, Pierre Vanderhaeghen
During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition.