Snail2 controls mesodermal BMP/Wnt induction of neural crest

Snail2 controls mesodermal BMP/Wnt induction of neural crest
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DOI:
10.1242/dev.064394
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发表时间:
2011-08
期刊:
影响因子:
4.6
通讯作者:
Jianli Shi;C. Severson;Jianxia Yang;D. Wedlich;M. Klymkowsky
Jianli Shi;C. Severson;Jianxia Yang;D. Wedlich;M. Klymkowsky
中科院分区:
生物学2区
文献类型:
--
作者:
Jianli Shi;C. Severson;Jianxia Yang;D. Wedlich;M. Klymkowsky

文献摘要

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神经嵴是脊椎动物特有的一种诱导组织。在爪蛙非洲爪蟾,神经嵴诱导依赖于信号分泌的预期背外侧中胚层区原肠胚形成。转录因子Snail 2(Slug)、Snail 1和Twist 1在该区域中表达。已知Snail 2和Twist 1是中胚层形成和神经嵴诱导所必需的。通过靶向卵裂球注射、基于吗啉代的功能丧失和外植体研究,我们发现:(1)Snail 1也是中胚层和神经嵴形成所必需的;(2)在32-细胞胚胎的C2/C3谱系中,snail 1、snail 2或twist 1功能的丧失阻碍了中胚层的形成,但神经嵴仅在snail 2功能丧失的情况下丧失;(3)snail 2突变体神经嵴的丧失涉及中胚层来源的分泌因子,并且可以通过bmp 4和wnt 8 RNA协同地拯救;和(4)snail 2活性的丧失导致许多BMP和Wnt激动剂和拮抗剂的RNA水平的变化。总之,这些结果确定蜗牛2作为一个关键的调节器的信号参与中胚层诱导神经嵴。
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.