PT  - JOURNAL ARTICLE
AU  - Sandra G. Gonzalez Malagon
AU  - Anna M. Lopez Muñoz
AU  - Daniel Doro
AU  - Triòna G. Bolger
AU  - Evon Poon
AU  - Elizabeth R. Tucker
AU  - Hadeel Adel Al-Lami
AU  - Matthias Krause
AU  - Christopher Phiel
AU  - Louis Chesler
AU  - Karen J. Liu
TI  - GSK3 Controls Migration of the Neural Crest Lineage
AID  - 10.1101/243170
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 243170
4099  - http://biorxiv.org/content/early/2018/01/04/243170.short
4100  - http://biorxiv.org/content/early/2018/01/04/243170.full
AB  - Migration of the neural crest lineage is critical to its physiological function. Mechanisms controlling neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here, we uncover novel requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in neural crest cells and that this activation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with pathologically increased ALK activity express high levels of pY-GSK3 and migration of these cells can be inhibited by GSK3 or ALK blockade. In normal neural crest cells, loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK-3 results in failure of migration. All together, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.