title: 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.
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Methot
authors.forename: Robert
authors.initials: R
authors.lastname: Hermann
authors.forename: Yeman
authors.initials: Y
authors.lastname: Tang
authors.forename: Rita
authors.initials: R
authors.lastname: Lo
authors.forename: Hosam
authors.initials: H
authors.lastname: Al-Jehani
authors.forename: Sumit
authors.initials: S
authors.lastname: Jhas
authors.forename: Devon
authors.initials: D
authors.lastname: Svoboda
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Slack
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barker
authors.forename: Stefano
authors.initials: S
authors.lastname: Stifani
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D019579:Neocortex / Q000166:cytology / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008156:Luciferases; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D051996:Transcription Factor RelA; C486570:Hes6 protein, mouse; C407737:Neurog3 protein, mouse; C498144:Rela protein, mouse