Embryo size regulates the timing and mechanism of pluripotent tissue morphogenesis.

Henrique Marques-Souza,Francesco Antonica,William Mansfield,Lorenzo C Orietti,Marta N Shahbazi,Christos Kyprianou,Viviane Souza Rosa,Magdalena Zernicka-Goetz

doi:10.1016/j.stemcr.2020.09.004

Abstract

SummaryMammalian 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 pro-amniotic 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.

Highlights

Mammalian development is regulative, as embryos are able to compensate for perturbations to the normal developmental program to ensure the formation of a viable organism (Lawrence and Levine, 2006; Tarkowski and Wroblewska, 1967)
Mammalian embryogenesis is a paradigm of regulative development as mouse embryos show plasticity in the regulation of cell fate, cell number, and tissue morphogenesis
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

Summary

Introduction

Mammalian development is regulative, as embryos are able to compensate for perturbations to the normal developmental program to ensure the formation of a viable organism (Lawrence and Levine, 2006; Tarkowski and Wroblewska, 1967). Mouse and human embryos comprise three cell lineages: embryonic epiblast that will give rise to the future organism; extra-embryonic primitive endoderm that will give rise to the yolk sac; and trophectoderm that will build the placenta. After embryo implantation, these three lineages interact to undertake the first morphogenetic step, remodeling of the epiblast from a group of apolar cells to a polarized epithelium that lines the incipient pro-amniotic cavity (Bedzhov and Zernicka-Goetz, 2014). This is an essential event for the establishment of the body plan and it becomes accomplished by embryonic day 5.0 (E5.0) (Shahbazi and Zernicka-Goetz, 2018; Sheng, 2015)

Results

Discussion

Conclusion