Mammalian Embryo: Establishment of the Embryonic Axes

Abstract

Owing to implantation and the requirement for extraembryonic tissues during mammalian embryogenesis, the development of the foetal axes is a relatively late event. Consequently, the definitive body axes of the organism are established in the founder tissue of the foetus well after polarised asymmetries have arisen in the conceptus. The anterior–posterior polarity of the organism has its origin in an extraembryonic tissue, the visceral endoderm, and there is evidence that the axes of the conceptus directly influence the orientation of the definitive body axes. Directional cell movements in the visceral endoderm help position the primitive streak, a structure that plays a key role in establishing the pattern of the primary body axis. Subsequently, asymmetries along the left–right axis are generated. As these are fundamental events that the remainder of embryonic development is predicated on, defects in these processes generally lead to embryos that fail to develop further.

Key Concepts

  • The mammalian embryo first generates structures and tissues that contribute to the placenta; therefore, there are various axes of asymmetry in the early conceptus that are not present in the final foetus.
  • There is a progressive increase in the degree of asymmetry in the pre‐implantation conceptus from an approximately spherically symmetrical zygote to radially symmetrical early blastocyst and finally bilaterally symmetrical late blastocyst.
  • The epiblast, which gives rise to the foetus, does not appear to have intrinsic axial information but receives axial patterning information from an extraembryonic tissue called the anterior visceral endoderm.
  • The anterior visceral endoderm defines the site of gastrulation by restricting the formation of the primitive streak in the epiblast.
  • The migratory movement of the anterior visceral endoderm is crucial to the proper orientation of the anterior–posterior axis.
  • A specialised structure called the node, located at the rostral end of the primitive streak, plays a central role not only in the organisation of the primary body axis but also in generating left–right asymmetries.

Keywords: mammalian embryo; mouse axis formation; blastocyst; anterior patterning; left–right asymmetry

Figure 1. (a, b) Development of the mouse embryo from fertilisation to gastrulation. At 3.5 days, the blastocyst forms and a clear proximo‐distal polarity is evident. The ovoid shape of the blastocyst means that there is also a plane of bilateral asymmetry. By 4.0 days, this axis has acquired polarity due to a distinct tilt in the profile of the inner cell mass (ICM). Two days after implantation and 6.5 days after fertilisation, gastrulation commences and the primitive streak forms at the embryonic–extraembryonic junction. Mesoderm is produced in the streak. The origin of the streak marks the posterior aspect of the future organism. By 7.5 days, the streak has elongated to the distal tip of the embryo and its anterior end has formed a specialised structure, the node. Axial mesendoderm emanates from the node and moves anteriorly to underly prospective neurectoderm. The axes of the future organism are explicit at 6.5 days and are shown superimposed on an adult mouse.
Figure 2. Manipulations of pre‐implantation embryos which suggest that the mammalian egg does not contain essential patterning cues for axis determination. (a) Development of a mouse from one cell of a two‐cell stage embryo. (b) Isolated single blastomeres from a four‐cell stage embryo form trophectoderm vesicles devoid of inner cell mass (ICM), but if aggregated with other blastomeres, they have the potential to form all the tissues of the blastocyst and of a liveborn mouse. (c) Juxtaposing two 8‐cell embryos results in their aggregation and formation of a single giant blastocyst that can give rise to a normal liveborn chimaeric mouse. (d) Normally, inside cells of a 16‐cell morula tend to form ICM, whereas outside cells form trophectoderm. Normal blastocysts can be made from exclusively inside or exclusively outside cells.
Figure 3. Diagram illustrating gene expression, cell lineage and time‐lapse microscopy studies which indicate that proximal–distal polarity of the implanting mouse embryo is transformed into anterior–posterior polarity by directional cell movement in the visceral endoderm. The arrows show the direction of AVE migration, whereas the flat‐headed arrows indicate the repressive influence of the AVE on the expression of primitive streak markers in the epiblast. continues to be expressed in the AVE at E5.75 and E6.5 but is not depicted for the sake of clarity. Similarly, markers such as are expressed in the epiblast before E5.5 but are not depicted for the sake of clarity.
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Srinivas, Shankar(Jan 2015) Mammalian Embryo: Establishment of the Embryonic Axes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000733.pub2]