title: Nuclear factor κB-dependent neurite remodeling is mediated by Notch pathway.
abstract: In this study, we evaluated whether a cross talk between nuclear factor κB (NF-κB) and Notch may take place and contribute to regulate cell morphology and/or neuronal network in primary cortical neurons. We found that lack of p50, either induced acutely by inhibiting p50 nuclear translocation or genetically in p50(-/-) mice, results in cortical neurons characterized by reduced neurite branching, loss of varicosities, and Notch1 signaling hyperactivation. The neuronal morphological effects found in p50(-/-) cortical cells were reversed after treatment with the γ-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-1-alanyl 1]-S-phenylglycine t-butyl ester) or Notch RNA interference. Together, these data suggested that morphological abnormalities in p50(-/-) cortical neurons were dependent on Notch pathway hyperactivation, with Notch ligand Jagged1 being a major player in mediating such effect. In this line, we demonstrated that the p50 subunit acts as transcriptional repressor of Jagged1. We also found altered distribution of Notch1 and Jagged1 immunoreactivity in the cortex of p50(-/-) mice compared with wild-type littermates at postnatal day 1. These data suggest the relevance of future studies on the role of Notch/NF-κB cross talk in regulating cortex structural plasticity in physiological and pathological conditions.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, University of Brescia, 25123 Brescia, Italy.
authors.forename: Sara Anna
authors.initials: SA
authors.lastname: Bonini
authors.forename: Giulia
authors.initials: G
authors.lastname: Ferrari-Toninelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Uberti
authors.forename: Mery
authors.initials: M
authors.lastname: Montinaro
authors.forename: Laura
authors.initials: L
authors.lastname: Buizza
authors.forename: Cristina
authors.initials: C
authors.lastname: Lanni
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Grilli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology; D052002:NF-kappa B p50 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D051881:Receptor, Notch1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1