Lumen Expansion Facilitates Epiblast-Primitive Endoderm Fate Specification during Mouse Blastocyst Formation.

Allyson Quinn Ryan,Takashi Hiiragi,François Graner,Chii Jou Chan

doi:10.1016/j.devcel.2019.10.011

Abstract

SummaryEpithelial tissues typically form lumina. In mammalian blastocysts, in which the first embryonic lumen forms, many studies have investigated how the cell lineages are specified through genetics and signaling, whereas potential roles of the fluid lumen have yet to be investigated. We discover that in mouse pre-implantation embryos at the onset of lumen formation, cytoplasmic vesicles are secreted into intercellular space. The segregation of epiblast and primitive endoderm directly follows lumen coalescence. Notably, pharmacological and biophysical perturbation of lumen expansion impairs the specification and spatial segregation of primitive endoderm cells within the blastocyst. Luminal deposition of FGF4 expedites fate specification and partially rescues the reduced specification in blastocysts with smaller cavities. Combined, our results suggest that blastocyst lumen expansion plays a critical role in guiding cell fate specification and positioning, possibly mediated by luminally deposited FGF4. Lumen expansion may provide a general mechanism for tissue pattern formation.

Highlights

Pre-implantation mouse development culminates with the formation of a blastocyst containing three spatially segregated cell lineages and an abembryonically localized fluid lumen
During the 32-cell stage, inner cells are stochastically biased toward either EPI or primitive endoderm (PrE) identity on a molecular level (Chazaud et al, 2006; Guo et al, 2010; Ohnishi et al, 2014; Schrode et al, 2014). These biases are reinforced or changed during the following blastocyst development depending on cell position within the inner cell mass (ICM), such that the EPI cells are surrounded by TE and PrE cells, which align along the luminal surface (Frankenberg et al, 2011; Plusa et al, 2008; Saiz et al, 2013)
Widespread Secretion of Cytoplasmic Vesicles into Intercellular Space Drives Early Fluid Accumulation Given the multipoint origin of the blastocyst lumen (Motosugi et al, 2005), we examined the first moments of extracellular fluid accumulation at high spatial resolution over multiple timescales (Figures 1A–1C)

Summary

Introduction

Pre-implantation mouse development culminates with the formation of a blastocyst containing three spatially segregated cell lineages and an abembryonically localized fluid lumen. During the 32-cell stage, inner cells are stochastically biased toward either EPI or PrE identity on a molecular level (Chazaud et al, 2006; Guo et al, 2010; Ohnishi et al, 2014; Schrode et al, 2014). These biases are reinforced or changed during the following blastocyst development depending on cell position within the ICM, such that the EPI cells are surrounded by TE and PrE cells, which align along the luminal surface (Frankenberg et al, 2011; Plusa et al, 2008; Saiz et al, 2013). Fibroblast growth factor (FGF) signaling plays a key role in establishing the molecular identity of ICM cells (Chazaud et al, 2006; Kang et al, 2013; Krawchuk et al, 2013; Ohnishi et al, 2014; Yamanaka et al, 2010) and signals to both ICM lineages (Kang et al, 2017; Molotkov et al, 2017) as well as the trophectoderm (Goldin and Papaioannou, 2003)

Methods

Results

Discussion

Conclusion