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, 51 (4), 219-33

Anatomy of a Blastocyst: Cell Behaviors Driving Cell Fate Choice and Morphogenesis in the Early Mouse Embryo


Anatomy of a Blastocyst: Cell Behaviors Driving Cell Fate Choice and Morphogenesis in the Early Mouse Embryo

Nadine Schrode et al. Genesis.


The preimplantation period of mouse early embryonic development is devoted to the specification of two extraembryonic tissues and their spatial segregation from the pluripotent epiblast. During this period two cell fate decisions are made while cells gradually lose their totipotency. The first fate decision involves the segregation of the extraembryonic trophectoderm (TE) lineage from the inner cell mass (ICM); the second occurs within the ICM and involves the segregation of the extraembryonic primitive endoderm (PrE) lineage from the pluripotent epiblast (EPI) lineage, which eventually gives rise to the embryo proper. Multiple determinants, such as differential cellular properties, signaling cues and the activity of transcriptional regulators, influence lineage choice in the early embryo. Here, we provide an overview of our current understanding of the mechanisms governing these cell fate decisions ensuring proper lineage allocation and segregation, while at the same time providing the embryo with an inherent flexibility to adjust when perturbed.


Figure 1
Figure 1. Overview of preimplantation development leading to blastocyst formation
Proper lineage segregation is ensured by two cell fate decisions. The first giving rise to trophectoderm and inner cell mass and the second leading to the allocation of primitive endoderm and epiblast. E: embryonic day. Of note, these cell fate decisions are schematized as being sequential but this may not strictly be the case.
Figure 2
Figure 2. Active gene regulatory networks throughout preimplantation development
For details, see text. Green: trophectoderm cells, blue: primitive endoderm cells, red: epiblast cells, purple: unspecified ICM cells, arrows: positive regulation, blocked arrows: negative regulation, circle arrows: autoregulation.
Figure 3
Figure 3. Model for trophectoderm lineage allocation
The prevailing model posits cell polarity cues and differential Hippo signaling activation. Outside cells are polarized, consequently Hippo signaling is inactive. YAP can be transported into the nucleus, where it co-activates Tead4 to drive expression of TE specific genes. Conversely, Hippo signaling in unpolarized inner cells results in phosphorylation and degradation of YAP leading to no co-activation of Tead4.
Figure 4
Figure 4. Working models for primitive endoderm lineage allocation
A Time inside - time outside model. Cells from the first wave of asymmetric divisions are biased to become EPI while cells from the second and third wave are biased to become PrE due to the further developed identity of their parental cells. B Stochastic model. Cells are unbiased by the wave of asymmetric divisions they arise from. Rather, stochastic fluctuations in gene expression direct cell identity in a random fashion. By comparison a Pdgfrα transcriptional reporter exhibits differential expression that can be classified into two subpopulations or PrE biased cells, prior to being expressed at high levels in all PrE cells and low levels or absent in EPI cells (dashed lines).

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