Interaction and antagonistic roles of NF-?B and Hes6 in the regulation of cortical neurogenesis.

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

SUBMITTER: Methot L 

PROVIDER: S-EPMC3700133 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other