RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development
RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development
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DOI：
10.1128/mcb.00319-06
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发表时间：
2006-07
影响因子：
5.3
通讯作者：
Céline Souilhol;Sarah Cormier;K. Tanigaki;C. Babinet;M. Cohen-Tannoudji
中科院分区：
文献类型：
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作者：
Céline Souilhol;Sarah Cormier;K. Tanigaki;C. Babinet;M. Cohen-Tannoudji
Notch信号通路是一个进化上保守的信号系统，已被证明在迄今研究的所有后生动物的细胞命运规范和胚胎发育的许多方面至关重要。我们最近证明Notch信号通路的几个组成部分，包括哺乳动物中已知的四种Notch受体及其五种配体，在小鼠卵母细胞、小鼠着床前胚胎或两者中表达。这提示Notch通路可能在小鼠胚胎分裂的第一个细胞命运规范中起作用，从而导致囊胚的形成。为了直接解决这一问题，我们产生了母系和合子都不表达Rbpsuh的受精卵，Rbpsuh是核心Notch信号通路的关键元素。我们发现这些受精卵产生的囊胚能够正常植入和发育。然而，在原肠胚形成后，这些胚胎在妊娠中期死亡，类似于Rbpsuh-null突变体。这表明rbp - j - κ依赖通路，也称为标准Notch通路，对于囊胚形态发生和外胚层、内胚层和中胚层三个胚层的建立是必不可少的。这些结果是根据最近的观察来讨论的，这些观察对这一结论提出了挑战。
ABSTRACT The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-Jκ-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.