Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways.
Gaber, Zachary B
Velez Bravo, Fausto D
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Bonnefont, J., Tiberi, L., Van Den Ameele, J., Potier, D., Gaber, Z. B., Lin, X., Bilheu, A., et al. (2019). Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways.. Neuron, 103 (6), 1096-1108.e4. https://doi.org/10.1016/j.neuron.2019.06.027
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.
Animals, Mice, Fibroblast Growth Factors, Histones, Gene Expression Profiling, Signal Transduction, Histone Code, Proto-Oncogene Proteins c-bcl-6, Receptors, Notch, Hedgehog Proteins, Neurogenesis, Sirtuin 1, Neural Stem Cells, Wnt Signaling Pathway, Epigenetic Repression, Cell Self Renewal, RNA-Seq
External DOI: https://doi.org/10.1016/j.neuron.2019.06.027
This record's URL: https://www.repository.cam.ac.uk/handle/1810/295239
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/