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Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation

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...

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Detalles Bibliográficos
Autores principales: McWilliams, Thomas G., Howard, Laura, Wyatt, Sean, Davies, Alun M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407286/
https://www.ncbi.nlm.nih.gov/pubmed/25753410
http://dx.doi.org/10.1016/j.celrep.2015.02.016
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author McWilliams, Thomas G.
Howard, Laura
Wyatt, Sean
Davies, Alun M.
author_facet McWilliams, Thomas G.
Howard, Laura
Wyatt, Sean
Davies, Alun M.
author_sort McWilliams, Thomas G.
collection PubMed
description 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.
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spelling pubmed-44072862015-04-26 Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation McWilliams, Thomas G. Howard, Laura Wyatt, Sean Davies, Alun M. Cell Rep Report 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. Cell Press 2015-03-05 /pmc/articles/PMC4407286/ /pubmed/25753410 http://dx.doi.org/10.1016/j.celrep.2015.02.016 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Report
McWilliams, Thomas G.
Howard, Laura
Wyatt, Sean
Davies, Alun M.
Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation
title Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation
title_full Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation
title_fullStr Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation
title_full_unstemmed Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation
title_short Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation
title_sort regulation of autocrine signaling in subsets of sympathetic neurons has regional effects on tissue innervation
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407286/
https://www.ncbi.nlm.nih.gov/pubmed/25753410
http://dx.doi.org/10.1016/j.celrep.2015.02.016
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