The p21-activated kinase Pak1 regulates induction and migration of the neural crest in Xenopus
The p21-activated kinase Pak1 regulates induction and migration of the neural crest in Xenopus
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DOI：
10.4161/cc.19685
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发表时间：
2012-04-01
期刊：
影响因子：
4.3
通讯作者：
Moss, Tom
中科院分区：
文献类型：
--
作者：
Bisson, Nicolas;Wedlich, Doris;Moss, Tom
Pak1 是丝氨酸/苏氨酸激酶 PAK 家族的成员，该家族是 Rac1 和 Cdc42 小 GTP 酶的下游效应子，与细胞骨架重组有关。 Pak1 在非洲爪蟾胚胎中的早期表达受到组织限制，这表明 Pak1 在器官发生和颅神经嵴 (CNC) 细胞迁移中发挥作用。通过观察体内和移植后的 CNC，我们发现显性失活 (DN) Pak1 抑制其迁移。 DN-Pak1 还特异性修饰了几个 NC 标记的表达。 Twist 表达减少，Snail1 表达后移，但 Snail2 (Slug)、Sox9 和 AP2 不受影响。 DN-Pak1 对 CNC 迁移的抑制可以用 Snail1 来挽救，但不能用 Twist 来挽救，事实上，Twist 与 DN-Pak1 合作抑制迁移。数据证实，单独的 Snail1 和 Snail2 表达都不足以满足非洲爪蟾 CNC 迁移的需要。此外，他们表明，在该组织中，Snail1 和 Snail2 的表达不是相互依赖的，这些因素也不受强制性的共同调节，并且它们的表达依赖于信号转导。我们的结果也代表了 Pak1 将细胞外信号与 CNC 规范所需的转录因子遗传级联联系起来的第一个证据。
Pak1 is a member of the PAK family of serine/threonine kinases that are downstream effectors of Rac1 and Cdc42 small GTPases and that are implicated in cytoskeleton reorganization. Early expression of Pak1 in Xenopus embryos is tissue restricted, suggesting a role in organogenesis and in cranial neural crest (CNC) cell migration. By observing CNC in vivo and after transplantation, we show that a dominant-negative (DN) Pak1 inhibits its migration. DN-Pak1 also specifically modified the expression of several NC markers. Twist expression was decreased and Snail1 expression posteriorized, but Snail2 (Slug), Sox9 and AP2 were unaffected. DN-Pak1 inhibition of CNC migration could be rescued with Snail1 but not with Twist, which, in fact, cooperated with DN-Pak1 in inhibiting migration. The data confirm that neither Snail1 nor Snail2 expression alone is sufficient for Xenopus CNC migration. Furthermore, they show that, in this tissue, Snail1 and Snail2 expression is not interdependent, nor are these factors subject to obligatory co-regulation, and that their expression depends on signal transduction. Our results also represent the first evidence that Pak1 links extracellular signals to the genetic cascade of transcription factors necessary for CNC specification.