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First published online 17 September 2009
doi: 10.1242/dev.035295

Development 136, 3405-3412 (2009)
Published by The Company of Biologists 2009
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Developmental switch in NF-{kappa}B signalling required for neurite growth

Núria Gavaldà, Humberto Gutierrez and Alun M. Davies*

Cardiff School of Biosciences, Biomedical Building, Museum Avenue, Cardiff CF10 3AT, Wales, UK.

* Author for correspondence (daviesalun{at}cf.ac.uk)

Accepted 13 August 2009

For a given cell type, particular extracellular signals generate characteristic patterns of activity in intracellular signalling networks that lead to distinctive cell-type specific responses. Here, we report the first known occurrence of a developmental switch in the intracellular signalling network required for an identical cellular response to the same extracellular signal in the same cell type. We show that although NF-{kappa}B signalling is required for BDNF-promoted neurite growth from both foetal and postnatal mouse sensory neurons, there is a developmental switch between these stages in the NF-{kappa}B activation mechanism and the phosphorylation status of the p65 NF-{kappa}B subunit required for neurite growth. Shortly before birth, BDNF activates NF-{kappa}B by an atypical mechanism that involves tyrosine phosphorylation of I{kappa}B{alpha} by Src family kinases, and dephosphorylates p65 at serine 536. Immediately after birth, BDNF-independent constitutive activation of NF-{kappa}B signalling by serine phosphorylation of I{kappa}B{alpha} and constitutive dephosphorylation of p65 at serine 536 are required for BDNF-promoted neurite growth. This abrupt developmental switch in NF-{kappa}B signalling in a highly differentiated cell type illustrates an unsuspected plasticity in signalling networks in the generation of identical cellular responses to the same extracellular signal.

Key words: NF-{kappa}B, Neurite growth, Signalling, BDNF, Sensory neuron


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