First cell lineage specification in mammalian early development

Abstract

Mouse pre-implantation embryogenesis is featured by several rounds of sequential cleavages, followed by the first cell lineage formation, specification of the inner cell mass (ICM) and trophectoderm (TE) at blastocyst stage. Establishment of the first cell lineage through asymmetric cell division is a longstanding question in developmental biology. Based on analogy to other lower model organisms or early achievements in mammalian development, three classic models of the first cell lineage specification are proposed to address this question: The prepattern or mosaic model, the inside-outside or positional model, and the polarization model. However, none of these models could well explain the highly regulatory nature of early mammalian embryos. During the past decades, great efforts have been made to elucidate when and how the pre-implantation blastomeres become different and finally segregate from each other. Mounting evidences show that the fate of trophectoderm is regulated by the Hippo/Yap/Tead signaling cascade in mouse early embryogenesis. In addition, single cell profiling and living imaging illustrate the great heterogeneity between blastomeres, providing some explanations for the regulatory nature of mammalian early embryos. Accompanying these progresses, a self-organization model was recently proposed to explain the blastocyst patterning in mammalian early embryos. This new model reconciles the experimental findings that seem to be contradictory to the three classic models and thus is regarded as a reformulation but improvement of classic models. Even so, however, the exact molecular mechanisms underlying this highly dynamic, complex and self-regulative process remain enigmatic. In this review, using mouse as the model system, we firstly summarize the preimplantation development and the classic models of the first cell lineage specification. Then, we highlight recent progresses, especially, the contributions of molecular regulators and heterogeneity of blastomeres in orchestrating the segregation of ICM and TE in mouse early embryos. At last, we summarize the current view on the first cell lineage specification in mammalian early embryogenesis and provide some clues for the future investigations. Altogether, the molecular basis of first cell lineage specification in mammals not only promotes the understanding for the beginning of life, but also contributes to stem cell biology and reproductive medicine.