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

作者：Malagon Sandra G Gonzalez; Munoz Anna M Lopez; Doro Daniel; Bolger Triona G; Poon Evon; Tucker Elizabeth R; Al Lami Hadeel Adel; Krause Matthias; Phiel Christopher J; Chesler Louis; Liu Karen J^*

来源：Nature Communications, 2018, 9(1): 1126.

DOI：10.1038/s41467-018-03512-5

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.

• 出版日期2018-3-19