Snail precedes Slug in the genetic cascade required for the specification and migration of the Xenopus neural crest
Snail precedes Slug in the genetic cascade required for the specification and migration of the Xenopus neural crest
复制标题
DOI：
10.1242/dev.00238
复制
发表时间：
2003-02-01
期刊：
影响因子：
4.6
通讯作者：
Mayor, R
中科院分区：
文献类型：
--
作者：
Aybar, MJ;Nieto, MA;Mayor, R
复杂的诱导事件序列负责在神经板和表皮之间的边界产生神经脊，触发涉及几个转录因子家族的遗传级联反应。蜗牛家族的两个成员，蜗牛和鼻涕，都与这一系列事件有关。在小鸡和非洲爪哇中，功能丧失和功能获得的实验已经提供了证据，表明鼻涕虫在神经脊的发育中起着关键作用。然而，与雏鸟不同，蜗牛而不是鼻涕虫在小鼠的迁移前神经脊中表达，在非洲爪哇中，蜗牛在这个种群中的表达先于鼻涕虫。因此，为了研究Snail在非洲爪哇神经脊发育中的作用，我们利用不同的Snail结构与糖皮质激素受体元件融合，进行了条件获得和功能丧失实验。我们发现，在指定的时间，Snail能够诱导Slug和所有其他被测试的神经脊标记(Zic5、FoxD3、Twist和Ets1)的表达。在没有神经板和中胚层标记的情况下，这种激活在整个胚胎和动物帽中都可以观察到。我们证明了Snail对于神经脊的指定和迁移是必需的，并且它作为转录抑制因子发挥作用。这些功能以前被归因于Slug。然而，Slug本身不能在动物CAP分析中诱导其他神经脊标记，我们证明了在过度表达研究中测试Snail和Slug时，它们在功能上是相同的。这表明，在非洲爪哇胚胎中，至少有一些以前被认为是鼻涕的功能可以由Snail来执行。另外，在注入显性-负结构的胚胎中的救援实验表明，Snail位于导致神经脊形成的遗传级联中鼻涕的上游，并在脊突的发育中发挥关键作用。
The complex sequence of inductive events responsible for the generation of the neural crest at the border between the neural plate and the epidermis, triggers a genetic cascade involving several families of transcription factors. Two members of the Snail family, Snail and Slug, have both been implicated in this cascade. In chick and Xenopus, loss- and gain-of-function experiments have provided evidence that Slug plays a key role in neural crest development. However, in contrast to the chick, Snail rather than Slug is expressed in the premigratory neural crest in the mouse and, in Xenopus, Snail precedes Slug expression in this population. Thus, in order to study the function of Snail in neural crest development in Xenopus, we have carried out conditional gain- and loss-of-function experiments using different Snail constructs fused to a glucocorticoid receptor element. We show that Snail is able to induce the expression of Slug and all other neural crest markers tested (Zic5, FoxD3, Twist and Ets1) at the time of specification. This activation is observed in whole embryos and in animal caps, in the absence of neural plate and mesodermal markers. We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. These functions have been previously attributed to Slug. However, Slug alone is unable to induce other neural crest markers in animal cap assays, and we show that Snail and Slug can be functionally equivalent when tested in overexpression studies. This suggests that, in Xenopus embryos, at least some of the functions previously attributed to Slug can be carried out by Snail. This is additionally supported by rescue experiments in embryos injected with dominant-negative constructs that indicate that Snail lies upstream of Slug in the genetic cascade leading to neural crest formation and that it plays a key role in crest development.