{"corpus_id":264665365,"paper_sha":"6c7a6e5b989979fe5b8b9416ddff20c4eff45af0","doi":"10.1038/s41467-018-03512-5","arxiv_id":null,"pmid":29555900,"pmcid":"5859133","mag_id":2791386712,"dblp_id":null,"acl_id":null,"title":"Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus","year":2018,"publication_date":"2018-03-19","venue":"Nature Communications","journal":{"name":"Nature Communications","pages":null,"volume":"9"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":88,"citation_count":38,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Anaplastic Lymphoma Kinase","mj":false,"qs":[{"q":"antagonists & inhibitors","mj":false,"ui":"Q000037"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D000077548"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Cell Line, Tumor","mj":false,"ui":"D045744"},{"d":"Cell Lineage","mj":false,"ui":"D019070"},{"d":"Cell Movement","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D002465"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Glycogen Synthase Kinase 3","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"deficiency","mj":false,"ui":"Q000172"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D038362"},{"d":"Glycogen Synthase Kinase 3 beta","mj":false,"qs":[{"q":"deficiency","mj":false,"ui":"Q000172"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D000071679"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Knockout","mj":false,"ui":"D018345"},{"d":"Neural Crest","mj":false,"qs":[{"q":"cytology","mj":true,"ui":"Q000166"},{"q":"embryology","mj":false,"ui":"Q000196"},{"q":"enzymology","mj":true,"ui":"Q000201"}],"ui":"D009432"},{"d":"Neuroblastoma","mj":false,"qs":[{"q":"enzymology","mj":false,"ui":"Q000201"}],"ui":"D009447"},{"d":"Phosphorylation","mj":false,"ui":"D010766"},{"d":"Pregnancy","mj":false,"ui":"D011247"},{"d":"Xenopus Proteins","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D029867"},{"d":"Xenopus laevis","mj":false,"qs":[{"q":"embryology","mj":false,"ui":"Q000196"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D014982"}],"chemicals":[{"n":"Xenopus Proteins","ui":"D029867","reg":"0"},{"n":"Anaplastic Lymphoma Kinase","ui":"D000077548","reg":"EC 2.7.10.1"},{"n":"Glycogen Synthase Kinase 3 beta","ui":"D000071679","reg":"EC 2.7.11.1"},{"n":"Gsk3b protein, mouse","ui":"C000605507","reg":"EC 2.7.11.1"},{"n":"GSK3B protein, Xenopus","ui":"C581760","reg":"EC 2.7.11.26"},{"n":"Glycogen Synthase Kinase 3","ui":"D038362","reg":"EC 2.7.11.26"},{"n":"glycogen synthase kinase 3 alpha","ui":"C448021","reg":"EC 2.7.11.26"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nature.com/articles/s41467-018-03512-5.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/6c7a6e5b989979fe5b8b9416ddff20c4eff45af0","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"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. Defects in neural crest development cause neurocristopathies and cancer, but what regulates this is unclear. Here, the authors show that glycogen synthase kinase 3 (GSK3) regulates migration of neural crest cells, as shown on genetic deletion of GSK3 in the mouse, and that this acts via anaplastic lymphoma kinase.","claims":[{"public_id":"cl_b5c28dbce0bd8941fa47d6a16f0bfa22","status":"active","text":"Genetic reduction of glycogen synthase kinase 3 causes failure of neural crest migration.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_b5c28dbce0bd8941fa47d6a16f0bfa22"},{"public_id":"cl_9fe59ecb5f104c9eec29cae3a5dae952","status":"active","text":"Glycogen synthase kinase 3 is required for neural crest cell migration in mouse and Xenopus models.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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