MKL/SRF and Bcl6 mutual transcriptional repression safeguards the fate and positioning of neocortical progenitor cells mediated by RhoA.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
17 11 2023
17 11 2023
Historique:
medline:
17
11
2023
pubmed:
15
11
2023
entrez:
15
11
2023
Statut:
ppublish
Résumé
During embryogenesis, multiple intricate and intertwined cellular signaling pathways coordinate cell behavior. Their slightest alterations can have dramatic consequences for the cells and the organs they form. The transcriptional repressor Bcl6 was recently found as important for brain development. However, its regulation and integration with other signals is unknown. Using in vivo functional approaches combined with molecular mechanistic analysis, we identified a reciprocal regulatory loop between B cell lymphoma 6 (Bcl6) and the RhoA-regulated transcriptional complex megakaryoblastic leukemia/serum response factor (MKL/SRF). We show that Bcl6 physically interacts with MKL/SRF, resulting in a down-regulation of the transcriptional activity of both Bcl6 and MKL/SRF. This molecular cross-talk is essential for the control of proliferation, neurogenesis, and spatial positioning of neural progenitors. Overall, our data highlight a regulatory mechanism that controls neuronal production and neocortical development and reveal an MKL/SRF and Bcl6 interaction that may have broader implications in other physiological functions and in diseases.
Identifiants
pubmed: 37967194
doi: 10.1126/sciadv.add0676
pmc: PMC10651131
doi:
Substances chimiques
Serum Response Factor
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadd0676Références
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