10779/crick.11559786.v1
Jerome Bonnefont
Jerome
Bonnefont
Luca Tiberi
Luca
Tiberi
Jelle van den Ameele
Jelle
van den Ameele
Delphine Potier
Delphine
Potier
Zachary B Gaber
Zachary B
Gaber
Xionghui Lin
Xionghui
Lin
Angéline Bilheu
Angéline
Bilheu
Adèle Herpoel
Adèle
Herpoel
Fausto D Velez Bravo
Fausto D Velez
Bravo
François Guillemot
François
Guillemot
Stein Aerts
Stein
Aerts
Pierre Vanderhaeghen
Pierre
Vanderhaeghen
Cortical neurogenesis requires Bcl6-mediated transcriptional repression of multiple self-renewal-promoting extrinsic pathways.
The Francis Crick Institute
2020
Bcl6
FGF signaling
Notch signaling
SHH signaling
Wnt signaling
brain development
cyclins
neurogenesis
stemness
transcription
Guillemot FC001089
AS-ack
Neurology & Neurosurgery
1109 Neurosciences
1702 Cognitive Sciences
1701 Psychology
2020-01-09 16:44:34
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Cortical_neurogenesis_requires_Bcl6-mediated_transcriptional_repression_of_multiple_self-renewal-promoting_extrinsic_pathways_/11559786
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.