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Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis
The developmental morphogen Sonic hedgehog (Shh) may continue to play a sustaining role in adult motor neurons, of potential relevance to motor neuron diseases including amyotrophic lateral sclerosis. The Shh signaling pathway is incompletely understood and interactions with other signaling pathways...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434959/ https://www.ncbi.nlm.nih.gov/pubmed/27984541 http://dx.doi.org/10.1097/WNR.0000000000000725 |
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author | Ma, Xiaoxing Drannik, Anna Jiang, Fan Peterson, Randy Turnbull, John |
author_facet | Ma, Xiaoxing Drannik, Anna Jiang, Fan Peterson, Randy Turnbull, John |
author_sort | Ma, Xiaoxing |
collection | PubMed |
description | The developmental morphogen Sonic hedgehog (Shh) may continue to play a sustaining role in adult motor neurons, of potential relevance to motor neuron diseases including amyotrophic lateral sclerosis. The Shh signaling pathway is incompletely understood and interactions with other signaling pathways are possible. We focus here on Notch, and first show that there is an almost linear reduction in light output from a Gli reporter in Shh Light II cells in the presence of increasing concentrations of the Notch inhibitor DAPT (r(2)=0.982). Second, in the spinal cord of mutant superoxide dismutase mice, but not control mice, a key marker of Notch signaling changes with age. Before the onset of clinical signs, the Notch intracellular domain is expressed predominantly in motor neurons, but by 125 days of age, Notch intracellular domain expression is markedly reduced in motor neurons and increased in neighboring astroglia. Third, there is a parallel reduction in Gli protein expression in mutant superoxide dismutase mouse spinal motor neurons, consistent with the observed reduction in Notch signaling and also a redistribution of Gli away from the nucleus. Thus, there is a reduction in motor neuronal Notch signaling and associated changes in Shh signaling, occurring coincidentally with disease expression, that may contribute toward the dysfunction and death of motor neurons in amyotrophic lateral sclerosis. |
format | Online Article Text |
id | pubmed-5434959 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-54349592017-05-23 Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis Ma, Xiaoxing Drannik, Anna Jiang, Fan Peterson, Randy Turnbull, John Neuroreport Degeneration and Repair The developmental morphogen Sonic hedgehog (Shh) may continue to play a sustaining role in adult motor neurons, of potential relevance to motor neuron diseases including amyotrophic lateral sclerosis. The Shh signaling pathway is incompletely understood and interactions with other signaling pathways are possible. We focus here on Notch, and first show that there is an almost linear reduction in light output from a Gli reporter in Shh Light II cells in the presence of increasing concentrations of the Notch inhibitor DAPT (r(2)=0.982). Second, in the spinal cord of mutant superoxide dismutase mice, but not control mice, a key marker of Notch signaling changes with age. Before the onset of clinical signs, the Notch intracellular domain is expressed predominantly in motor neurons, but by 125 days of age, Notch intracellular domain expression is markedly reduced in motor neurons and increased in neighboring astroglia. Third, there is a parallel reduction in Gli protein expression in mutant superoxide dismutase mouse spinal motor neurons, consistent with the observed reduction in Notch signaling and also a redistribution of Gli away from the nucleus. Thus, there is a reduction in motor neuronal Notch signaling and associated changes in Shh signaling, occurring coincidentally with disease expression, that may contribute toward the dysfunction and death of motor neurons in amyotrophic lateral sclerosis. Lippincott Williams & Wilkins 2017-02-08 2017-05-18 /pmc/articles/PMC5434959/ /pubmed/27984541 http://dx.doi.org/10.1097/WNR.0000000000000725 Text en Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Degeneration and Repair Ma, Xiaoxing Drannik, Anna Jiang, Fan Peterson, Randy Turnbull, John Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
title | Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
title_full | Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
title_fullStr | Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
title_full_unstemmed | Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
title_short | Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
title_sort | crosstalk between notch and sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis |
topic | Degeneration and Repair |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434959/ https://www.ncbi.nlm.nih.gov/pubmed/27984541 http://dx.doi.org/10.1097/WNR.0000000000000725 |
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