Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus.
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Embargo End Date
ICR Authors
Authors
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
Lopez Muñoz, AM
Doro, D
Bolger, TG
Poon, E
Tucker, ER
Adel Al-Lami, H
Krause, M
Phiel, CJ
Chesler, L
Liu, KJ
Document Type
Journal Article
Date
2018-03-19
Date Accepted
2018-02-20
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.
Citation
Nature communications, 2018, 9 (1), pp. 1126 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2041-1723
eISSN
2041-1723
Research Team
Paediatric Solid Tumour Biology and Therapeutics