Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Development. 2011 Aug;138(15):3135-45. doi: 10.1242/dev.064394. Epub 2011 Jun 29.
The neural crest is an induced tissue that is unique to vertebrates. In the clawed frog Xenopus laevis, neural crest induction depends on signals secreted from the prospective dorsolateral mesodermal zone during gastrulation. The transcription factors Snail2 (Slug), Snail1 and Twist1 are expressed in this region. It is known that Snail2 and Twist1 are required for both mesoderm formation and neural crest induction. Using targeted blastomere injection, morpholino-based loss of function and explant studies, we show that: (1) Snail1 is also required for mesoderm and neural crest formation; (2) loss of snail1, snail2 or twist1 function in the C2/C3 lineage of 32-cell embryos blocks mesoderm formation, but neural crest is lost only in the case of snail2 loss of function; (3) snail2 mutant loss of neural crest involves mesoderm-derived secreted factors and can be rescued synergistically by bmp4 and wnt8 RNAs; and (4) loss of snail2 activity leads to changes in the RNA levels of a number of BMP and Wnt agonists and antagonists. Taken together, these results identify Snail2 as a key regulator of the signals involved in mesodermal induction of neural crest.
神经嵴是一种仅存在于脊椎动物中的诱导组织。在爪蟾 Xenopus laevis 中,神经嵴的诱导取决于原肠胚形成期间来自未来背侧中胚层区域的信号分泌。转录因子 Snail2(Slug)、Snail1 和 Twist1 在该区域表达。已知 Snail2 和 Twist1 对于中胚层形成和神经嵴诱导都是必需的。通过靶向卵裂球注射、基于 morpholino 的功能丧失和外植体研究,我们表明:(1)Snail1 对于中胚层和神经嵴形成也是必需的;(2)在 32 细胞胚胎的 C2/C3 谱系中丧失 snail1、snaill2 或 twist1 功能会阻止中胚层形成,但仅在 snaill2 功能丧失的情况下才会失去神经嵴;(3)snaill2 突变体神经嵴的丧失涉及中胚层衍生的分泌因子,并且可以通过 bmp4 和 wnt8 RNA 协同拯救;(4)丧失 snaill2 活性会导致大量 BMP 和 Wnt 激动剂和拮抗剂的 RNA 水平发生变化。综上所述,这些结果表明 Snail2 是参与中胚层诱导神经嵴的信号的关键调节剂。