Plasticity of the inner cell mass in mouse blastocyst is restricted by the activity of FGF/MAPK pathway

Wigger, Magdalena; Kisielewska, Katarzyna; Filimonow, Katarzyna; Płusa, Berenika; Maleszewski, Marek; Suwińska, Aneta

doi:10.1038/s41598-017-15427-0

Cited by 41 publications

(39 citation statements)

References 56 publications

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“…Our results show that the global positional features (see Terminology Box) of NANOG and GATA6 in early blastocysts do not show a pattern. This lack of a pattern might allow for the previously observed plasticity during the cell fate decision process [22,28,64,65].…”

Section: A Global Pattern Of Nanog and Gata6 Expression In The Icm Stmentioning

confidence: 99%

The transition from local to global patterns governs the differentiation of mouse blastocysts

et al. 2020

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During mammalian blastocyst development, inner cell mass (ICM) cells differentiate into epiblast (Epi) or primitive endoderm (PrE). These two fates are characterized by the expression of the transcription factors NANOG and GATA6, respectively. Here, we investigate the spatio-temporal distribution of NANOG and GATA6 expressing cells in the ICM of the mouse blastocysts with quantitative three-dimensional single cell-based neighbourhood analyses. We define the cell neighbourhood by local features, which include the expression levels of both fate markers expressed in each cell and its neighbours, and the number of neighbouring cells. We further include the position of a cell relative to the centre of the ICM as a global positional feature. Our analyses reveal a local three-dimensional pattern that is already present in early blastocysts: 1) Cells expressing the highest NANOG levels are surrounded by approximately nine neighbours, while 2) cells expressing GATA6 cluster according to their GATA6 levels. This local pattern evolves into a global pattern in the ICM that starts to emerge in mid blastocysts. We show that FGF/MAPK signalling is involved in the threedimensional distribution of the cells and, using a mutant background, we further show that the GATA6 neighbourhood is regulated by NANOG. Our quantitative study suggests that the three-dimensional cell neighbourhood plays a role in Epi and PrE precursor specification. Our results highlight the importance of analysing the three-dimensional cell neighbourhood while investigating cell fate decisions during early mouse embryonic development.

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Section: A Global Pattern Of Nanog and Gata6 Expression In The Icm Stmentioning

confidence: 99%

The transition from local to global patterns governs the differentiation of mouse blastocysts

et al. 2020

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“…The authors propose that lumen expansion is needed for correct lineage segregation ( Ryan et al, 2019 ). Interestingly, in isolated ICMs, epiblast and PE progenitors segregate, although with an increased proportion of PE to epiblast cells ( Wigger et al, 2017 ). This result suggests that, although the second cell fate decision can take place in the absence of the blastocoel, it may be required to fine-tune the relative numbers of epiblast and PE progenitors.…”

Section: The Implanting Embryo: a Global Transformationmentioning

confidence: 99%

Mechanisms of human embryo development: from cell fate to tissue shape and back

2020

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Gene regulatory networks and tissue morphogenetic events drive the emergence of shape and function: the pillars of embryo development. Although model systems offer a window into the molecular biology of cell fate and tissue shape, mechanistic studies of our own development have so far been technically and ethically challenging. However, recent technical developments provide the tools to describe, manipulate and mimic human embryos in a dish, thus opening a new avenue to exploring human development. Here, I discuss the evidence that supports a role for the crosstalk between cell fate and tissue shape during early human embryogenesis. This is a critical developmental period, when the body plan is laid out and many pregnancies fail. Dissecting the basic mechanisms that coordinate cell fate and tissue shape will generate an integrated understanding of early embryogenesis and new strategies for therapeutic intervention in early pregnancy loss.

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“…To identify a simplified system to study this lineage segregation, we first confirmed, as shown in (18), that pEPI and pPrE cells in ICMs isolated from E3.5 or E3.75 blastocysts can segregate and commit to EPI and PrE in culture without trophectoderm (Fig. S2a).…”

Section: R a F Tmentioning

confidence: 78%

Cell surface fluctuations regulate early embryonic lineage sorting

Yanagida

Revell

Stirparo

et al. 2020

Preprint

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In development, lineage segregation of multiple lineages must be coordinated in time and space. An important example is the mammalian inner cell mass (ICM), in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the foetus). The physical mechanisms that determine this spatial segregation between EPI and PrE are still poorly understood. Here, we identify an asymmetry in cell-cell affinity, a mechanical property thought to play a significant role in tissue sorting in other systems, between EPI and PrE precursors (pEPI and pPrE). However, a computational model of cell sorting indicated that these differences alone appeared insufficient to explain the spatial segregation. We also observed significantly greater surface fluctuations in pPrE compared to pEPI. Including the enhanced surface fluctuation in pPrE in our simulation led to robust cell sorting. We identify phospho-ERM regulated membrane tension as an important mediator of the increased surface fluctuations in pPrE. Using aggregates of engineered cell lines with different surface fluctuation levels cells with higher surface fluctuations were consistently excluded to the outside of the aggregate. These cells behaved similarly when incorporated in the embryo. Surface fluctuations-driven segregation is reminiscent of activity-induced phase separation, a sorting phenomenon in colloidal physics. Together, our experiments and model identify dynamic cell surface fluctuations, in addition to static mechanical properties, as a key factor for orchestrating the correct spatial positioning of the founder embryonic lineages.

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Plasticity of the inner cell mass in mouse blastocyst is restricted by the activity of FGF/MAPK pathway

Cited by 41 publications

References 56 publications

The transition from local to global patterns governs the differentiation of mouse blastocysts

The transition from local to global patterns governs the differentiation of mouse blastocysts

Mechanisms of human embryo development: from cell fate to tissue shape and back

Cell surface fluctuations regulate early embryonic lineage sorting

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