Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus.
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Date
2018-03-19Author
Gonzalez Malagon, SG
Lopez Muñoz, AM
Doro, D
Bolger, TG
Poon, E
Tucker, ER
Adel Al-Lami, H
Krause, M
Phiel, CJ
Chesler, L
Liu, KJ
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Cell Line, Tumor
Neural Crest
Animals
Mice, Knockout
Xenopus laevis
Humans
Mice
Neuroblastoma
Glycogen Synthase Kinase 3
Xenopus Proteins
Cell Movement
Phosphorylation
Cell Lineage
Pregnancy
Female
Glycogen Synthase Kinase 3 beta
Anaplastic Lymphoma Kinase
Research team
Paediatric Solid Tumour Biology and Therapeutics
Language
eng
Date accepted
2018-02-20
License start date
2018-03-19
Citation
Nature communications, 2018, 9 (1), pp. 1126 - ?
Publisher
NATURE PUBLISHING GROUP