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.

中文翻译：

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糖原合酶激酶 3 控制小鼠和非洲爪蟾中神经嵴谱系的迁移。

神经嵴迁移对其生理功能至关重要。由于难以在体内访问该细胞群，控制哺乳动物神经嵴迁移的机制相对未知。在这里，我们报告了在非洲爪蟾和小鼠模型中调节神经嵴的糖原合酶激酶 3 (GSK3) 的要求。我们证明 GSK3 在小鼠神经嵴细胞中被酪氨酸磷酸化 (pY)，而 GSK3 的缺失导致 pFAK 增加以及 Rac1 和 lamellipodin（细胞迁移的关键调节因子）的失调。GSK3的遗传减少导致迁移失败。我们发现 pY-GSK3 磷酸化取决于间变性淋巴瘤激酶 (ALK)，这是一种与神经母细胞瘤相关的蛋白质。与此一致，ALK 活性增加的神经母细胞瘤细胞表达高水平的 pY-GSK3，GSK3 或 ALK 的阻断会影响这些细胞的迁移。总之，这项工作确定了 GSK3 在神经嵴发育和癌症期间细胞迁移中的作用。