The Apical Domain Is Required and Sufficient for the First Lineage Segregation in the Mouse Embryo

Korotkevich, Ekaterina; Niwayama, Ritsuya; Courtois, Aurélien; Friese, Stefanie; Berger, Nicolas; Buchholz, Frank; Hiiragi, Takashi

doi:10.1016/j.devcel.2017.01.006

Cited by 196 publications

(255 citation statements)

References 52 publications

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“…Notably, the fixed timing of cavitation, reported by Korotkevich et al [88], suggests that the timing of TE/ICM differentiation may also start at fertilization. In our model, the timing of TE/ICM differentiation is flexible and only requires a defined time point when polarity is defined.…”

Section: Resultsmentioning

confidence: 99%

Four simple rules that are sufficient to generate the mammalian blastocyst

et al. 2017

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Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, and environmental interactions to generate the physical arrangement of the blastocyst with precise timing. However, this process occurs in the absence of maternal information and in the presence of transcriptional stochasticity. How does the preimplantation embryo ensure robust, reproducible development in this context? It utilizes a versatile toolbox that includes complex intracellular networks coupled to cell—cell communication, segregation by differential adhesion, and apoptosis. Here, we ask whether a minimal set of developmental rules based on this toolbox is sufficient for successful blastocyst development, and to what extent these rules can explain mutant and experimental phenotypes. We implemented experimentally reported mechanisms for polarity, cell—cell signaling, adhesion, and apoptosis as a set of developmental rules in an agent-based in silico model of physically interacting cells. We find that this model quantitatively reproduces specific mutant phenotypes and provides an explanation for the emergence of heterogeneity without requiring any initial transcriptional variation. It also suggests that a fixed time point for the cells’ competence of fibroblast growth factor (FGF)/extracellular signal—regulated kinase (ERK) sets an embryonic clock that enables certain scaling phenomena, a concept that we evaluate quantitatively by manipulating embryos in vitro. Based on these observations, we conclude that the minimal set of rules enables the embryo to experiment with stochastic gene expression and could provide the robustness necessary for the evolutionary diversification of the preimplantation gene regulatory network.

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Section: Resultsmentioning

confidence: 99%

Four simple rules that are sufficient to generate the mammalian blastocyst

et al. 2017

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“…During the 8 to 16 cell divisions, cells inherit varying amounts of apically localized proteins from the apical domain – the polarized outside surface forming at the 8 cell stage (Anani et al, 2014; Johnson and Ziomek, 1981; Korotkevich et al, 2017; Watanabe et al, 2014). Inside cells are apolar, while outside cells can either be apolar or polar.…”

Section: Introductionmentioning

confidence: 99%

Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

Pósfai

Petropoulos

Barros

et al. 2017

eLife

146

153

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The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling.DOI: http://dx.doi.org/10.7554/eLife.22906.001

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“…It has been demonstrated that polarization is necessary and sufficient for YAP nuclear localization, CDX2 expression, and trophoblast differentiation in mice (Cockburn et al, ; Hirate et al, ; Korotkevich et al, ). Thus, we speculated that the asynchronous CDX2 expression pattern in porcine trophoblast cells may be the result of an asynchronous polarization process in the trophoblast.…”

Section: Resultsmentioning

confidence: 99%

Asynchronous CDX2 expression and polarization of porcine trophoblast cells reflects a species‐specific trophoderm lineage determination progress model

Liu

Bou

Zhao

et al. 2018

Molecular Reproduction Devel

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Upregulation of Cdx2 expression in outer cells is a key event responsible for cell lineage segregation between the inner cell mass and the trophoderm (TE) in mouse morula-stage embryos. In TE cells, polarization can regulate Hippo and Rho-associated kinase (Rho-ROCK) signaling to induce the nuclear location of YAP, which has been demonstrated to further induce the expression of Cdx2. However, we found that CDX2 expression could not be detected in the outer cells of porcine morula-stage embryos but only in some TE cells at the early blastocyst stage. The biological significance and the regulation mechanism of this species-specific CDX2 expression pattern have still not been determined. We show here that an asynchronous CDX2 expression pattern exists in porcine TE cells during the development of the blastocyst. We demonstrate that CDX2 expression in porcine TE cells depends on the nuclear localization of YAP and polarization of the embryo through Y27632 treatment. We found that the polarization process in the morula to the late blastocyst stage porcine embryos was asynchronous, which was revealed by the apical localization of phosphorylated EZRIN staining. Artificially enhancing the number of polarized blastomeres by culturing the separated blastomeres of four-cell stage porcine embryos resulted in increased CDX2-positive cell numbers. These results indicate that the mechanism of CDX2 expression regulation is conserved, but the polarization progress is not conserved between the pig and the mouse, and results in a species-specific trophoblast determination progress model.

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The Apical Domain Is Required and Sufficient for the First Lineage Segregation in the Mouse Embryo

Cited by 196 publications

References 52 publications

Four simple rules that are sufficient to generate the mammalian blastocyst

Four simple rules that are sufficient to generate the mammalian blastocyst

Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

Asynchronous CDX2 expression and polarization of porcine trophoblast cells reflects a species‐specific trophoderm lineage determination progress model

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