Cell fate decisions and axis determination in the early mouse embryo

Abstract

SummaryThe mouse embryo generates multiple cell lineages, as well as its future body axes in the early phase of its development. The early cell fate decisions lead to the generation of three lineages in the pre-implantation embryo: the epiblast, the primitive endoderm and the trophectoderm. Shortly after implantation, the anterior-posterior axis is firmly established. Recent studies have provided a better understanding of how the earliest cell fate decisions are regulated in the preimplantation embryo, and how and when the body axes are established in the pregastrulation embryo. In this review, we address the timing of the first cell fate decisions and of the establishment of embryonic polarity, and we ask how far back one can trace their origins. Key words: AP axis, Blastocyst, Cell fate, Trophectoderm, Inner cell mass, Primitive endoderm IntroductionThe early development of the mouse embryo, from a fertilized egg to a gastrulating embryo, involves a tightly regulated series of lineage specification events and the simultaneous establishment of the embryonic axes (Fig. 1). These events include the formation of a blastocyst, following compaction (see Glossary, Box 1) at embryonic day (E) 3.5, when cells then go on to form either the trophectoderm (TE, see Glossary, Box 1) or inner cell mass (ICM), from which the epiblast (Epi, see Glossary, Box 1) or primitive endoderm (PrE, see Glossary, Box 1) are subsequently derived.Given that the mouse embryo begins life as one cell, the fertilized egg must perform at least three tasks during the early phase of development. It must: (1) increase the number of cells by proliferation; (2) increase the number of cell types by differentiation; and (3) generate polarity to allow the establishment of the future body axis. How can an embryo generate multiple types of cells and polarities when it starts out as a single cell? Where do the initial signals for the induction of cell differentiation and for the generation of asymmetries come from?Diverse mechanisms to establish early polarity are known to operate in various organisms (Kloc and Etkin, 2005;Schneider and Bowerman, 2003;St Johnston, 2005), but let us think of two extreme scenarios (Fig. 2). In one scenario, there is a determinant in a specific region of the oocyte, and this determinant becomes asymmetrically distributed after fertilization. This determinant can thus be inherited asymmetrically as the fertilized egg divides. A blastomere that receives this determinant will adopt a cell fate that is different from a blastomere that does not receive the determinant, resulting in the generation of two cell types or of a polarity within the embryo. Bicoid in Drosophila (Huynh and St Johnston, 2004) and Macho-1 in ascidians (Nishida and Sawada, 2001) are examples of such determinants. In the second scenario, the embryo does not have such a localized maternal determinant, so it must make use of some other signal(s) to generate polarity and different cell types.The current view is that the mouse embryo probably conforms to the se...

A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis

“…We conclude that the genes maintained in a transcriptionally poised state in fetal germ cells are developmental regulators. This class includes genes essential for specification of a complete conceptus, including the embryo proper, trophectoderm, and primitive endoderm (28).…”

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

“…However, the output of this interaction seems to depend on the cellular context as Nodal transcripts are abnormally downregulated in the epiblast and in the primitive streak of E6.5 N1ICD epi embryos, and ectopically expressed in proximal anterior ectoderm and mesoderm from E7.5. In the wild-type embryo, fine-tuning of NODAL signalling is essential to orchestrate proliferation, migration and specification of embryonic and extraembryonic cell types during anterior-posterior polarity establishment, primitive streak formation, gastrulation, and leftright patterning (reviewed by Robertson, 2014;Shiratori and Hamada, 2014;Takaoka and Hamada, 2012). In agreement with its major role during early embryonic patterning, Nodal expression is extremely dynamic and tightly regulated by positive and negative inputs integrated on enhancer sequences.…”

“…The proximodistal polarity of the E5.5 embryo is transformed into anterior-posterior polarity at E6.5 through the migration of DVE cells from distal to anterior positions, where they take the name of anterior visceral endoderm cells (AVE), and the formation of the primitive streak in the posterior epiblast (reviewed by Rossant and Tam, 2009;Takaoka and Hamada, 2012). The transcription factor brachyury (T ) marked the posterior epiblast and the nascent primitive streak both in control and N1ICD epi littermates (n=3; Fig.…”

Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos

“…The embryonic lineage is pluripotent and will give rise to the fetus, while the extra-embryonic lineages will differentiate into supportive structures critical for embryo implantation and fetal development, the placenta, and yolk sac (Takaoka and Hamada, 2012;Zernicka-Goetz et al, 2009). How and when these lineages start to separate in morphologically homogenous cells has been very difficult to dissect in mammals.…”