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CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation

CD40‐activated CD40L reverse signaling is a major physiological regulator of the growth of neural processes in the developing nervous system. Previous work on superior cervical ganglion (SCG) neurons of the paravertebral sympathetic chain has shown that CD40L reverse signaling enhances NGF‐promoted...

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Detalles Bibliográficos
Autores principales: Calhan, Osman Yipkin, Wyatt, Sean, Davies, Alun Millward
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187455/
https://www.ncbi.nlm.nih.gov/pubmed/32077240
http://dx.doi.org/10.1002/dneu.22735
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author Calhan, Osman Yipkin
Wyatt, Sean
Davies, Alun Millward
author_facet Calhan, Osman Yipkin
Wyatt, Sean
Davies, Alun Millward
author_sort Calhan, Osman Yipkin
collection PubMed
description CD40‐activated CD40L reverse signaling is a major physiological regulator of the growth of neural processes in the developing nervous system. Previous work on superior cervical ganglion (SCG) neurons of the paravertebral sympathetic chain has shown that CD40L reverse signaling enhances NGF‐promoted axon growth and tissue innervation. Here we show that CD40L reverse signaling has the opposite function in prevertebral ganglion (PVG) sympathetic neurons. During a circumscribed perinatal window of development, PVG neurons cultured from Cd40 (–/–) mice had substantially larger, more exuberant axon arbors in the presence of NGF than PVG neurons cultured from wild‐type mice. Tissues that receive their sympathetic innervation from PVG neurons were markedly hyperinnervated in Cd40 (–/–) mice compared with wild‐type mice. The exuberant axonal growth phenotype of cultured CD40‐deficient perinatal PVG neurons was pared back to wild‐type levels by activating CD40L reverse signaling with a CD40‐Fc chimeric protein, but not by activating CD40 forward signaling with CD40L. The co‐expression of CD40 and CD40L in PVG neurons suggests that these proteins engage in an autocrine signaling loop in these neurons. Our work shows that CD40L reverse signaling is a physiological regulator of NGF‐promoted sympathetic axon growth and tissue innervation with opposite effects in paravertebral and prevertebral neurons.
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spelling pubmed-71874552020-04-29 CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation Calhan, Osman Yipkin Wyatt, Sean Davies, Alun Millward Dev Neurobiol Research Articles CD40‐activated CD40L reverse signaling is a major physiological regulator of the growth of neural processes in the developing nervous system. Previous work on superior cervical ganglion (SCG) neurons of the paravertebral sympathetic chain has shown that CD40L reverse signaling enhances NGF‐promoted axon growth and tissue innervation. Here we show that CD40L reverse signaling has the opposite function in prevertebral ganglion (PVG) sympathetic neurons. During a circumscribed perinatal window of development, PVG neurons cultured from Cd40 (–/–) mice had substantially larger, more exuberant axon arbors in the presence of NGF than PVG neurons cultured from wild‐type mice. Tissues that receive their sympathetic innervation from PVG neurons were markedly hyperinnervated in Cd40 (–/–) mice compared with wild‐type mice. The exuberant axonal growth phenotype of cultured CD40‐deficient perinatal PVG neurons was pared back to wild‐type levels by activating CD40L reverse signaling with a CD40‐Fc chimeric protein, but not by activating CD40 forward signaling with CD40L. The co‐expression of CD40 and CD40L in PVG neurons suggests that these proteins engage in an autocrine signaling loop in these neurons. Our work shows that CD40L reverse signaling is a physiological regulator of NGF‐promoted sympathetic axon growth and tissue innervation with opposite effects in paravertebral and prevertebral neurons. John Wiley and Sons Inc. 2020-02-29 2019 /pmc/articles/PMC7187455/ /pubmed/32077240 http://dx.doi.org/10.1002/dneu.22735 Text en © 2020 The Authors. Developmental Neurobiology published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Calhan, Osman Yipkin
Wyatt, Sean
Davies, Alun Millward
CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
title CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
title_full CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
title_fullStr CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
title_full_unstemmed CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
title_short CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
title_sort cd40l reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187455/
https://www.ncbi.nlm.nih.gov/pubmed/32077240
http://dx.doi.org/10.1002/dneu.22735
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