Suppression of ERK signalling abolishes primitive endoderm formation but does not promote pluripotency in rabbit embryo.

Anna Piliszek,Zofia E Madeja,Berenika Plusa

doi:10.1242/dev.156406

Abstract

Formation of epiblast (EPI) – the founder line of all embryonic lineages – and extra-embryonic supportive tissues is one of the key events in mammalian development. The prevailing model of early mammalian development is based almost exclusively on the mouse. Here, we provide a comprehensive, stage-by-stage analysis of EPI and extra-embryonic primitive endoderm (PrE) formation during preimplantation development of the rabbit. Although we observed that rabbit embryos have several features in common with mouse embryos, including a stage-related initiation of lineage specification, our results demonstrate the existence of some key differences in lineage specification among mammals. Contrary to the current view, our data suggest that reciprocal repression of GATA6 and NANOG is not fundamental for the initial stages of PrE versus EPI specification in mammals. Furthermore, our results provide insight into the observed discrepancies relating to the role of FGF/ERK signalling in PrE versus EPI specification between mouse and other mammals.

Highlights

Preimplantation development in the mammalian embryo is characterised by two consecutive cell fate specification events
Our observations established that EPI versus primitive endoderm (PrE) differentiation and sorting in the rabbit embryos takes place in blastocysts consisting of ∼100-1000 cells (3-4 dpc, stage VIIX)
Very few functional studies on PrE versus EPI specification in species other than the mouse have been performed to date (Boroviak et al, 2015; Kuijk et al, 2012; Roode et al, 2012; Nakamura et al, 2016)

Summary

Introduction

Preimplantation development in the mammalian embryo is characterised by two consecutive cell fate specification events. The apolar inner cells are displaced to one side of the embryo by the expansion of the fluidfilled cavity and form the inner cell mass (ICM) (Smith and McLaren, 1977). TE gives rise to the embryonic part of the placenta, whereas ICM cells further differentiate into two lineages: the pluripotent epiblast (EPI) and a second extra-embryonic lineage, the primitive endoderm (PrE) ( called hypoblast). EPI cells are the precursor lineage for the embryo proper, whereas PrE cells give rise to endoderm of the yolk sac and contribute to definitive endoderm later in development (reviewed by Chazaud and Yamanaka, 2016).

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