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Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus
Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural c...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859133/ https://www.ncbi.nlm.nih.gov/pubmed/29555900 http://dx.doi.org/10.1038/s41467-018-03512-5 |
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author | Gonzalez Malagon, Sandra G. Lopez Muñoz, Anna M. Doro, Daniel Bolger, Triòna G. Poon, Evon Tucker, Elizabeth R. Adel Al-Lami, Hadeel Krause, Matthias Phiel, Christopher J. Chesler, Louis Liu, Karen J. |
author_facet | Gonzalez Malagon, Sandra G. Lopez Muñoz, Anna M. Doro, Daniel Bolger, Triòna G. Poon, Evon Tucker, Elizabeth R. Adel Al-Lami, Hadeel Krause, Matthias Phiel, Christopher J. Chesler, Louis Liu, Karen J. |
author_sort | Gonzalez Malagon, Sandra G. |
collection | PubMed |
description | Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest in Xenopus and mouse models. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in mouse neural crest cells and that loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK3 results in failure of migration. We find that pY-GSK3 phosphorylation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with increased ALK activity express high levels of pY-GSK3, and blockade of GSK3 or ALK can affect migration of these cells. Altogether, this work identifies a role for GSK3 in cell migration during neural crest development and cancer. |
format | Online Article Text |
id | pubmed-5859133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58591332018-03-21 Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus Gonzalez Malagon, Sandra G. Lopez Muñoz, Anna M. Doro, Daniel Bolger, Triòna G. Poon, Evon Tucker, Elizabeth R. Adel Al-Lami, Hadeel Krause, Matthias Phiel, Christopher J. Chesler, Louis Liu, Karen J. Nat Commun Article Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest in Xenopus and mouse models. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in mouse neural crest cells and that loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK3 results in failure of migration. We find that pY-GSK3 phosphorylation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with increased ALK activity express high levels of pY-GSK3, and blockade of GSK3 or ALK can affect migration of these cells. Altogether, this work identifies a role for GSK3 in cell migration during neural crest development and cancer. Nature Publishing Group UK 2018-03-19 /pmc/articles/PMC5859133/ /pubmed/29555900 http://dx.doi.org/10.1038/s41467-018-03512-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gonzalez Malagon, Sandra G. Lopez Muñoz, Anna M. Doro, Daniel Bolger, Triòna G. Poon, Evon Tucker, Elizabeth R. Adel Al-Lami, Hadeel Krause, Matthias Phiel, Christopher J. Chesler, Louis Liu, Karen J. Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus |
title | Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus |
title_full | Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus |
title_fullStr | Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus |
title_full_unstemmed | Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus |
title_short | Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus |
title_sort | glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and xenopus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859133/ https://www.ncbi.nlm.nih.gov/pubmed/29555900 http://dx.doi.org/10.1038/s41467-018-03512-5 |
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