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

Research output: Contribution to journalArticlepeer-review

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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 languageEnglish
Article number1126
Number of pages15
JournalNature Communications
Volume9
Issue number1
Early online date19 Mar 2018
DOIs
Publication statusE-pub ahead of print - 19 Mar 2018

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