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Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade
Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is r...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983660/ https://www.ncbi.nlm.nih.gov/pubmed/29695045 http://dx.doi.org/10.3390/ijms19051266 |
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author | Dumoulin, Alexandre Ter-Avetisyan, Gohar Schmidt, Hannes Rathjen, Fritz G. |
author_facet | Dumoulin, Alexandre Ter-Avetisyan, Gohar Schmidt, Hannes Rathjen, Fritz G. |
author_sort | Dumoulin, Alexandre |
collection | PubMed |
description | Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception. |
format | Online Article Text |
id | pubmed-5983660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59836602018-06-05 Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade Dumoulin, Alexandre Ter-Avetisyan, Gohar Schmidt, Hannes Rathjen, Fritz G. Int J Mol Sci Review Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception. MDPI 2018-04-24 /pmc/articles/PMC5983660/ /pubmed/29695045 http://dx.doi.org/10.3390/ijms19051266 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Dumoulin, Alexandre Ter-Avetisyan, Gohar Schmidt, Hannes Rathjen, Fritz G. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade |
title | Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade |
title_full | Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade |
title_fullStr | Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade |
title_full_unstemmed | Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade |
title_short | Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade |
title_sort | molecular analysis of sensory axon branching unraveled a cgmp-dependent signaling cascade |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983660/ https://www.ncbi.nlm.nih.gov/pubmed/29695045 http://dx.doi.org/10.3390/ijms19051266 |
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