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Regulation of autocrine signaling in subsets of sympathetic neurons has regional effects on tissue innervation

McWilliams, Thomas G., Howard, Laura, Wyatt, Sean ORCID: and Davies, Alun M. ORCID: 2015. Regulation of autocrine signaling in subsets of sympathetic neurons has regional effects on tissue innervation. Cell Reports 10 (9) , pp. 1443-1449. 10.1016/j.celrep.2015.02.016

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The regulation of innervation by target-derived factors like nerve growth factor (NGF) is the cornerstone of neurotrophic theory. Whereas autocrine signaling in neurons affecting survival and axon growth has been described, it is difficult to reconcile autocrine signaling with the idea that targets control their innervation. Here, we report that an autocrine signaling loop in developing mouse sympathetic neurons involving CD40L (TNFSF5) and CD40 (TNFRSF5) selectively enhances NGF-promoted axon growth and branching, but not survival, via CD40L reverse signaling. Because NGF negatively regulates CD40L and CD40 expression, this signaling loop operates only in neurons exposed to low levels of NGF. Consequently, the sympathetic innervation density of tissues expressing low NGF is significantly reduced in CD40-deficient mice, whereas the innervation density of tissues expressing high levels of NGF is unaffected. Our findings reveal how differential regulation of autocrine signaling in neurons has region-specific effects on axon growth and tissue innervation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Additional Information: This is an open access article under the terms of the CC-BY Attribution 4.0 International license.
Publisher: Elsevier
ISSN: 2211-1247
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 2 February 2015
Last Modified: 03 May 2023 09:30

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