title: A role for the canonical nuclear factor-κB pathway in coupling neurotrophin-induced differential survival of developing spiral ganglion neurons.
abstract: Neurotrophins are key players of neural development by controlling cell death programs. However, the signaling pathways that mediate their selective responses in different populations of neurons remain unclear. In the mammalian cochlea, sensory neurons differentiate perinatally into type I and II populations both expressing TrkB and TrkC, which bind respectively brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3). How these two neuronal populations respond differentially to these two neurotrophins remains unknown. Here, we report in rat the segregation of the nuclear factor-κB (NFκB) subunit p65 specifically within the type II population postnatally. Using dissociated cultures of embryonic and postnatal spiral ganglion neurons, we observed a specific requirement of NFκB for BDNF but not NT3-dependent neuronal survival during a particular postnatal time window that corresponds to a period of neuronal cell death and hair cell innervation refinement in the developing cochlea. Consistently, postnatal p65 knockout mice showed a specific decreased number in type II spiral ganglion neurons. Taken together, these results identify NFκB as a type II neuron-specific factor that participates in the selective survival effects of BDNF and NT3 signaling on developing spiral ganglion neurons.
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée-Neurosciences, Developmental Neurobiology Unit, University of Liège Liège, Belgium.
authors.forename: Renaud
authors.initials: R
authors.lastname: Vandenbosch
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée-Neurosciences, Developmental Neurobiology Unit, University of Liège Liège, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Chocholova
authors.affiliation: Department of Human Genetics, University of Liège Liège, Belgium ; Groupe Interdisciplinaire de Génoprotéomique Appliquée-Research Center, University of Liège Liège, Belgium.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Robe
authors.affiliation: Department of Neuroscience, Karolinska Institute Stockholm, Sweden.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Bone and Cartilage Research Unit, Institute of Pathology, Centre Hospitalier Universitaire du Sart-Tilman Liège, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Lambert
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée-Neurosciences, Developmental Neurobiology Unit, University of Liège Liège, Belgium ; Department of Neurology, Centre Hospitalier Universitaire du Sart Tilman Liège, Belgium.
authors.forename: Gustave
authors.initials: G
authors.lastname: Moonen
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée-Neurosciences, Developmental Neurobiology Unit, University of Liège Liège, Belgium ; Department of Neuroscience, Karolinska Institute Stockholm, Sweden.
authors.forename: François
authors.initials: F
authors.lastname: Lallemend
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée-Neurosciences, Developmental Neurobiology Unit, University of Liège Liège, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée-Neurosciences, Developmental Neurobiology Unit, University of Liège Liège, Belgium ; Department of Neuroscience, Karolinska Institute Stockholm, Sweden.
authors.forename: Saïda
authors.initials: S
authors.lastname: Hadjab
keywords: NF-κB; cochlea; development; neuronal survival; neurotrophins; spiral ganglion neurons