Embryo size regulates the timing and mechanism of pluripotent tissue morphogenesis

Abstract

Mammalian embryogenesis is a paradigm of regulative development as mouse embryos show plasticity in the regulation of cell fate, cell number, and tissue morphogenesis. However, the mechanisms behind embryo plasticity remain largely unknown. Here, we determine how mouse embryos respond to an increase in cell numbers to regulate the timing and mechanism of embryonic morphogenesis, leading to the formation of the pro-amniotic cavity. Using embryos and embryonic stem cell aggregates of different size, we show that while proamniotic cavity formation in normal-sized embryos is achieved through basement membrane-induced polarization and exocytosis, cavity formation of increased-size embryos is delayed and achieved through apoptosis of cells that lack contact with the basement membrane. Importantly, blocking apoptosis, both genetically and pharmacologically, alters pro-amniotic cavity formation but does not affect size regulation in enlarged embryos. We conclude that the regulation of embryonic size and morphogenesis, albeit concomitant, have distinct molecular underpinnings.

Archetypal Architecture Construction, Patterning, and Scaling Invariance in a 3D Embryoid Body Differentiation Model

“…Multiple apoptotic and necrotic cells were identified using live-cell analysis of caspase activity (Cas) and with propidium iodide (PI) and Hoechst 33342 staining in the EB5 ( Figure 2E ). Additionally, we identified the small cell rosettes with the lumen ( Figures 1D3 , 2F2 ), which resembled those during the pro-amniotic cavity formation ( Bedzhov and Zernicka-Goetz, 2014 ; Orietti et al, 2021 ). These observations suggest that the EB central cavity may form through mixed mechanisms—apoptotic and hollowing-like ( Datta et al, 2011 )—in different local sites ( Figure 2F ).…”

All models are wrong, but some are useful: Establishing standards for stem cell-based embryo models

“…Finally, the physical characteristics of the model, such as the size, shape, and stiffness are also important considerations. Further investigation is needed to determine how they impact developmental processes (for example Orietti et al, 2020 ).…”

The mystery of monozygotic twinning II: What can monozygotic twinning tell us about Amyoplasia from a review of the various mechanisms and types of monozygotic twinning?

“…A few comments about what is known concerning human early embryologic development help lay the background for understanding MZ twinning and its relationships to RCEM and Amyoplasia. Early human development progresses in a hierarchical, self‐organizing cranial–caudal progression, with apparently the right side developing slightly ahead of the left side once various axes have been established (Denker, 2004; Klimczewska et al, 2018; Orietti et al, 2020). There appears to be some flexibility in the timing of human development, but MZ twins would be expected to be slightly behind singleton development.…”