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, TNF alpha can both promote and inhibit neurite growth depending on the cellular context. Specifically, transmembrane TNF alpha promotes neurite growth, while soluble TNF alpha inhibits it. While the growth promoting effects of TNF alpha are restricted to a defined developmental window of early postnatal development, whether the growth inhibitory effects of soluble TNF alpha 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 TNF alpha are restricted to a specific period of late embryonic and early postnatal development. Furthermore, we show that this growth inhibitory effect of soluble TNF alpha requires NF-kappa B signalling at all developmental stages at which soluble TNF alpha inhibits neurfie growth. These findings raise the possibility that increases in the amount of soluble TNF alpha in vivo, for example as a result of maternal inflammation, could negatively affect neurfic growth in developing neurons at specific stages of development. (C) 2015 International Society of Differentiation. Published by Elsevier BY. All tights reserved.