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TNF? reverse signaling promotes sympathetic axon growth and target innervation.

ABSTRACT: Reverse signaling via members of the tumor necrosis factor (TNF) superfamily controls multiple aspects of immune function. Here we document TNF? reverse signaling in the nervous system to our knowledge for the first time and show that it has a crucial role in establishing sympathetic innervation. During postnatal development, sympathetic axons express TNF? as they grow and branch in their target tissues, which in turn express TNF receptor 1 (TNFR1). In culture, soluble forms of TNFR1 act directly on postnatal sympathetic axons to promote growth and branching by a mechanism that depends on membrane-integrated TNF? and on downstream activation of ERK. Sympathetic innervation density is substantially lower in several tissues in postnatal and adult mice lacking either TNF? or TNFR1. These findings reveal that target-derived TNFR1 acts as a reverse-signaling ligand for membrane-integrated TNF? to promote growth and branching of sympathetic axons.

SUBMITTER: Kisiswa L

PROVIDER: S-EPMC3785146 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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TNFα reverse signaling promotes sympathetic axon growth and target innervation.

Kisiswa Lilian L Osório Catarina C Erice Clara C Vizard Thomas T Wyatt Sean S Davies Alun M AM

Nature neuroscience 20130609 7

Reverse signaling via members of the tumor necrosis factor (TNF) superfamily controls multiple aspects of immune function. Here we document TNFα reverse signaling in the nervous system to our knowledge for the first time and show that it has a crucial role in establishing sympathetic innervation. During postnatal development, sympathetic axons express TNFα as they grow and branch in their target tissues, which in turn express TNF receptor 1 (TNFR1). In culture, soluble forms of TNFR1 act directl ...[more]

PMID: 23749144

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