Interaction and Antagonistic Roles of NF-κB and Hes6 in the Regulation of Cortical Neurogenesis

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.

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SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01610-12.

ACKNOWLEDGMENTS

This work was supported by grants from the Canadian Institutes of Health Research to P.A.B. and S.S. (MOP-13957 and MOP-42479). P.A.B. and S.S. held Chercheur National Awards from the Fonds de la Recherche en Santé du Québec.

We thank T. Tetsuka for plasmids, R. Kageyama for anti-Hes1 antibody, M. Maira for assistance during electroporation studies, N. Unsain for assistance with NF-κB^LacZ mice, and M. Bouchard-Levasseur, S. Perrino, and I. Murillo for excellent animal care.