| Autor: |
Gonzalez Malagon SG; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK., Lopez Muñoz AM; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK., Doro D; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK., Bolger TG; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK., Poon E; Paediatric Solid Tumour Biology, Institute of Cancer Research/Royal Marsden NHS Trust, Surrey, SM2 5NG, UK., Tucker ER; Paediatric Solid Tumour Biology, Institute of Cancer Research/Royal Marsden NHS Trust, Surrey, SM2 5NG, UK., Adel Al-Lami H; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK., Krause M; Randall Division of Cell & Molecular Biophysics, King's College London, London, SE1 1UL, UK., Phiel CJ; Department of Integrative Biology, University of Colorado Denver, Denver, CO, 80204, USA., Chesler L; Paediatric Solid Tumour Biology, Institute of Cancer Research/Royal Marsden NHS Trust, Surrey, SM2 5NG, UK., Liu KJ; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK. karen.liu@kcl.ac.uk. |
| Abstrakt: |
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. |
