title: The neurite growth inhibitory effects of soluble TNFα on developing sympathetic neurons are dependent on developmental age.
abstract: During development, the growth of neural processes is regulated by an array of cellular and molecular mechanisms which influence growth rate, direction and branching. Recently, many members of the TNF superfamily have been shown to be key regulators of neurite growth during development. The founder member of this family, TNFα can both promote and inhibit neurite growth depending on the cellular context. Specifically, transmembrane TNFα promotes neurite growth, while soluble TNFα inhibits it. While the growth promoting effects of TNFα are restricted to a defined developmental window of early postnatal development, whether the growth inhibitory effects of soluble TNFα occur throughout development is unknown. In this study we used the extensively studied, well characterised neurons of the superior cervical ganglion to show that the growth inhibitory effects of soluble TNFα are restricted to a specific period of late embryonic and early postnatal development. Furthermore, we show that this growth inhibitory effect of soluble TNFα requires NF-κB signalling at all developmental stages at which soluble TNFα inhibits neurite growth. These findings raise the possibility that increases in the amount of soluble TNFα in vivo, for example as a result of maternal inflammation, could negatively affect neurite growth in developing neurons at specific stages of development.
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Nolan
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Collins
authors.affiliation: Molecular Biosciences Research Division, Life Sciences Building, School of Biosciences, Museum Avenue, Cardiff CF10 3AT, UK.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Wyatt
authors.affiliation: University of Lincoln, Brayford Pool, Lincoln, Lincolnshire LN6 7TS, UK. Electronic address: hgutierrez@lincoln.ac.uk.
authors.forename: Humberto
authors.initials: H
authors.lastname: Gutierrez
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland. Electronic address: g.okeeffe@ucc.ie.
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: Axonal growth; Innervation; NF-κB; Neuronal development; TNFα