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

The involvement of nuclear factor kappa B (NF-kappa B) 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-kappa B during embryonic brain development. It is shown here that NF-kappa B is selectively activated in neocortical neural progenitor cells in the developing mouse telencephalon. Blockade of NF-kappa B activity leads to premature cortical neuronal differentiation and depletion of the progenitor cell pool. Conversely, NF-kappa B 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-kappa B complexes in cortical progenitor cells. In turn, NF-kappa B 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-kappa B and Hes6 during cortical neurogenesis.