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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.
We thank T. Honjo (Kyoto, Japan) for the RBP-Jκf/f mice and B. Knowles (Bar Harbor, Maine) and D. Solter (Freiburg, Germany) for the ZP3-Cretg/tg transgenic line. We thank S. Tajbakhsh for critical reading of the manuscript.
This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Association pour la Recherche contre le Cancer (ARC), the Institut Pasteur GPH07 on stem cells, and the Agence Nationale pour la Recherche (contract number 05-JC05-41835). S.C. received grants from the Pasteur-Negri-Weizmann Council and the ARC. C.S. received grants from CNRS (Bourse de Doctorat pour les Ingénieurs).