Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse

Abstract

The investigation into lineage allocation and early asymmetries in the pre-and peri-implantation mouse embryo is gaining momentum. As we review here, new insights have been gained into the cellular and molecular events that lead to the establishment of the three lineages of the blastocyst, to the determination of the origin and the fates of the visceral endoderm in the peri-implantation mouse embryo, and to the generation of cellular and molecular activities that accompany the emergence of asymmetries in the pre-gastrulation embryo. We also discuss the continuing debate that surrounds the relative impacts of early lineage bias versus the stochastic allocation of cells with respect to the events that pattern the blastocyst and initiate its later asymmetries. IntroductionThe progression of the mammalian embryo from fertilization to gastrulation involves an ordered series of lineage specifications and axial asymmetries (Fig. 1) that result, first, in the development of the blastocyst (see Glossary, Box 1), with its embryonic-abembryonic axis ( Fig. 1; Box 2), and, later, in the formation of the embryo itself, with its anterior-posterior (AP), dorsal-ventral (DV) and left-right (LR) axes. In many invertebrates and vertebrates, asymmetries that are established in the egg correlate with the segregation of determinants that influence later lineage formation and axis development. However, in the mouse egg, the morphological asymmetries that exist, such as the position of the second polar body (see Glossary, Box 1) and the sperm entry point, do not clearly demarcate an asymmetric domain of, for example, signaling activity or of cell fate determinants in the fertilized mouse egg. Whether there is any instructive relationship between the asymmetry of the egg and the later asymmetry of the blastocyst and lineage allocation remains a controversial issue. It is well known that the pre-implantation mammalian embryo is highly regulative and resistant to the loss or addition of cells brought about by experimental manipulations. However, this does not preclude the existence of an, as yet, uncharacterized property that could bias developmental outcomes in the intact embryo.Whether any early asymmetries in the mouse egg and/or blastocyst relate to the orientation of the definitive body axes is even less certain. It is now clear that the AP patterning of the gastrulating embryo is initiated prior to gastrulation by spatially localized signals that emanate from regionally patterned extra-embryonic tissues. Some of these asymmetries may be set up as early as the blastocyst stage, linking pre-implantation patterning to post-implantation morphogenesis.Here, we review recent experiments that define the molecular components of lineage specification in the mouse blastocyst. We also review the ongoing uncertainty and debate that surrounds the relative importance of early cleavage patterns at the two-to four-cell stage and of symmetric versus asymmetric divisions at the eight-to 16-and 16-to 32-cell stage, and the importance of final cell po...

Importance of Methionine Metabolism in Morula-to-blastocyst Transition in Bovine Preimplantation Embryos

“…As a result, we found that OCT4 and CDX2 mRNA expression in day 6 compacted morulae were not different among the treatment groups. In murine embryos, it has been shown that Oct4 is required for specifying the pluripotent cells of the ICM, that Cdx2 is required for the commitment, integrity and differentiation of TE lineage and that these two transcription factors mutually suppress the expression of each other and contribute to establishment of the ICM and TE lineage [27]. The present results showed that the deficiency of methionine metabolism did not affect the expression of OCT4 and CDX2.…”

“…At the morula-to-blastocyst transition, mammalian embryos undergo the first lineage segregation into the inner cell mass (ICM) and trophectoderm (TE) [27,28]. The repression of morula-to-blastocyst transition by ethionine prompted us to investigate the expression levels of cell lineagerelated transcription factors involved in blastocyst formation.…”

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

“…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.…”

Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos

“…7f). At E6.2, mouse embryos establish the anterior VE (AVE), a specific repertoire of the VE 39 . The AVE expresses and secretes the Cerl and Lefty-1, which suppress Nodal signalling in the epiblast.…”