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Cleavage pattern and emerging asymmetry of the mouse embryo

Key Points

  • The development of the mouse embryo is regulative rather than determinative. However, development does not necessarily occur at random, as some initial bias or order can influence how cell fate becomes increasingly restricted over time. The orientation of cell divisions becomes progressively more influential in directing cells to positions that will affect their developmental properties.

  • The first cleavage division orientation is not determined but is not random — it is influenced by the zygote shape that changes on fertilization and by the position of the previous meiosis (animal pole).

  • The second cleavage divisions tend to occur orthogonally. If the first is meridional with respect to the animal pole and the second equatorial/oblique, it is possible to predict the fate of 4-cell blastomeres in the blastocyst.

  • Chimaeras that are made entirely of blastomeres destined to form the abembryonic parts of such blastocysts often fail in development, in contrast to chimaeras that are constructed from blastomeres destined to become the embryonic parts.

  • Asymmetrically oriented cell divisions at the 8–16-cell and 16–32-cell stages direct cells to the inside of the embryo to become inner cell mass. Those remaining on the outside develop into trophectoderm. Whether division is symmetric or asymmetric depends on the PAR protein complex.

  • The embryonic–abembryonic axis of the blastocyst is defined by the position of its cavity that forms in the abembryonic part. Two recent models are discussed: the cavity becomes positioned in response to differential pressure reflecting the shape of the zona; or the cavity is positioned adjacent to a group of cells that undergo symmetric cleavages and therefore are not directed to the inside.

  • Therefore, the orientations of successive cleavage divisions have consequences on cell-fate decisions that establish the first cell lineages and influence patterning of the early mouse embryo.

Abstract

Early mammalian development is regulative — it is flexible and responsive to experimental intervention. This flexibility could be explained if embryogenesis were originally completely unbiased and disordered; order and determination of cells only arising later. Alternatively, regulative behaviour could be consistent with the embryo having some order or bias from the very beginning, with inflexibility and cell determination increasing steadily over time. Recent evidence supports the second view and indicates that the sequence and the orientations of cell divisions help to build the first asymmetries.

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Figure 1: Fertilized mouse egg.
Figure 2: Cell shape influences orientation of the first cleavage division.
Figure 3: Relative order of meridional (M) and equatorial/oblique (E) second cleavages and spatial patterning of the blastocyst.
Figure 4: The fate and developmental properties of blastomeres of ME embryos.
Figure 5: Models of blastocyst formation.

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Acknowledgements

I am grateful for the contributions made by current and past collaborators and members of my laboratory and for support to my laboratory from the Wellcome Trust, Biotechnology and Biological Sciences Research Council (BBSRC) and European Molecular Biology Organization young investigator (EMBO YIP) award. I apologize to those whose work has gone unmentioned owing to space limitations.

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DATABASES

Swiss-Prot

aPKC

JAM1

PAR3

FURTHER INFORMATION

Magdalena Zernicka-Goetz's laboratory

Glossary

DETERMINANTS

Spatially localized factors that direct the fate of a cell.

ANIMAL POLE

The part of the egg where the meiotic divisions have occurred.

VEGETAL POLE

The opposite pole of the egg to the animal pole.

BLASTOMERES

Cells of the early-cleavage-stage embryo.

INNER CELL MASS

Inside cells of the blastocyst that retain pluripotency and give rise to all cell types of the future body.

TROPHECTODERM

First differentiated lineage of cells that surrounds the inner cell mass (ICM) in the blastocyst.

BLASTOCYST

An early stage of embryonic development, during which cells begin to commit to developmental lineages. It consists of two lineages — inner cell mass and trophectoderm.

COMPACTION

A process that is unique to mammalian embryonic cleavage, in which blastomeres flatten and become arranged closely together after the third cleavage to form a compact sphere.

POLAR BODY

A small cell that is extruded from the oocyte during meiosis and contains a discarded set of chromosomes. The first polar body often degenerates, while the second often stays attached to the embryo and is used as a marker of the animal pole.

FERTILIZATION CONE

The actin-rich protrusion that forms transiently on the egg on fertilization at the site of the sperm entry where the male chromatin is in the vicinity of the cell cortex.

PRONUCLEI

Haploid nuclei (female- and male-derived) of the zygote.

MORULA

The compacted embryo before cavity formation.

ZYGOTE

Embryo at the one-cell stage between fertilization and the first cell division. Often also referred to as a (fertilized) egg.

POLAR TROPHECTODERM

Trophectoderm that surrounds the inner cell mass (ICM).

MURAL TROPHECTODERM

Trophectoderm that surrounds blastocyst cavity.

ZONA PELLUCIDA

The glycoprotein coat that surrounds oocytes and the early embryos of mammals.

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Zernicka-Goetz, M. Cleavage pattern and emerging asymmetry of the mouse embryo. Nat Rev Mol Cell Biol 6, 919–928 (2005). https://doi.org/10.1038/nrm1782

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