Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus

Sandra G. Gonzalez Malagon; Anna M. Lopez Muñoz; Daniel Doro; Triòna G. Bolger; Evon Poon; Elizabeth R. Tucker; Hadeel Adel Al-Lami; Matthias Krause; Christopher J. Phiel; Louis Chesler; Karen J. Liu

doi:10.1038/s41467-018-03512-5

Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus

Sandra G. Gonzalez Malagon, Anna M. Lopez Muñoz, Daniel Doro, Triòna G. Bolger, Evon Poon, Elizabeth R. Tucker, Hadeel Adel Al-Lami, Matthias Krause, Christopher J. Phiel, Louis Chesler, Karen J. Liu^*

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	1126
Number of pages	15
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	19 Mar 2018
DOIs	https://doi.org/10.1038/s41467-018-03512-5
Publication status	E-pub ahead of print - 19 Mar 2018

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Glycogen synthase kinase GONZALEZ MALAGON Accepted 20Feb2018 GOLD VoR CCBYFinal published version, 12.2 MBLicence: CC BY

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Gonzalez Malagon, S. G., Lopez Muñoz, A. M., Doro, D., Bolger, T. G., Poon, E., Tucker, E. R., Adel Al-Lami, H., Krause, M., Phiel, C. J., Chesler, L., & Liu, K. J. (2018). Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus. Nature Communications, 9(1), Article 1126. Advance online publication. https://doi.org/10.1038/s41467-018-03512-5

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title = "Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus",

abstract = "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.",

author = "{Gonzalez Malagon}, {Sandra G.} and {Lopez Mu{\~n}oz}, {Anna M.} and Daniel Doro and Bolger, {Tri{\`o}na G.} and Evon Poon and Tucker, {Elizabeth R.} and {Adel Al-Lami}, Hadeel and Matthias Krause and Phiel, {Christopher J.} and Louis Chesler and Liu, {Karen J.}",

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AU - Gonzalez Malagon, Sandra G.

AU - Lopez Muñoz, Anna M.

AU - Doro, Daniel

AU - Bolger, Triòna G.

AU - Poon, Evon

AU - Tucker, Elizabeth R.

AU - Adel Al-Lami, Hadeel

AU - Krause, Matthias

AU - Phiel, Christopher J.

AU - Chesler, Louis

AU - Liu, Karen J.

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N2 - 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.

AB - 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.

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VL - 9

JO - Nature Communications

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ER -

Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus

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