Interaction and antagonistic roles of nf-κb and hes6 in the regulation of cortical neurogenesis

Laurent Methot, Robert Hermann, Yeman Tang, Rita Lo, Hosam Al-Jehani, Sumit Jhas, Philip A. Barker, Stefano Stifani, Devon Svoboda, Ruth S. Slack

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The involvement of nuclear factor kappa B (NF-κB) in several processes in the postnatal and adult brain, ranging from neuronal survival to synaptogenesis and plasticity, has been documented. In contrast, little is known about the functions of NF-κB during embryonic brain development. It is shown here that NF-κB is selectively activated in neocortical neural progenitor cells in the developing mouse telencephalon. Blockade of NF-κB activity leads to premature cortical neuronal differentiation and depletion of the progenitor cell pool. Conversely, NF-κB activation causes decreased cortical neurogenesis and expansion of the progenitor cell compartment. These effects are antagonized by the proneuronal transcription factor Hes6, which physically and functionally interacts with RelA-containing NF-κB complexes in cortical progenitor cells. In turn, NF-κB exerts an inhibitory effect on the ability of Hes6 to promote cortical neuronal differentiation. These results reveal previously uncharacterized functions and modes of regulation for NF-κB and Hes6 during cortical neurogenesis.

Original languageEnglish (US)
Pages (from-to)2797-2808
Number of pages12
JournalMolecular and Cellular Biology
Volume33
Issue number14
DOIs
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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