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  • Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways.

Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways.

Neuron (2019-07-30)
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
ABSTRACT

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.

MATERIALS
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Product Description

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CNQX, ≥98% (HPLC), solid
Sigma-Aldrich
OptiPrep Density Gradient Medium, used for cell and subcellular organelle isolation
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Anti-acetyl-Histone H1.4 (Ac-Lys26) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
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Triptolide, from Tripterygium wilfordii, ≥98% (HPLC), solid
Roche
DIG RNA Labeling Kit (SP6/T7), sufficient for 2 x 10 labeling reactions, kit of 1 (12 components), suitable for hybridization, suitable for Southern blotting
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Ethyl alcohol, Pure, 200 proof, for molecular biology
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Triton X-100, laboratory grade
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2-Propanol, BioUltra, for molecular biology, ≥99.5% (GC)