The free-living stage of our development ends with implantation in the uterus. As mammals, implanting in the uterine wall is a requirement for us to develop. An early step in this process is the formation of the basketball like (but much much smaller, about 100µm, or the size of a fine grain of sand!) spherical structure called a blastocyst.
Several posts ago we discussed how the fertilized egg divides into 2 embryonic cells or blastomeres, and how they then divide to 4 and then 8 cells. We said those divisions were symmetrical or nearly so with the cells dividing at more or less the same time and forming identical daughter cells. When the 8 cell morula stage compacts we noted the divisions became asymmetrical resulting in polar and apolar cells [read our previous post on asymmetry during compaction here], but the embryo itself remains symmetrical, that is there is no right or left side and no up or down. The next step creates an embryo that has an axis, it is asymmetrical with one pole of the sphere called the embryonic pole getting ready to make the fetus.
The late morula stage after compaction [you can read more about compaction here] acquires an eccentrically placed, silt-like fluid-filled structure, the blastocoel. The process of blastulation (the formation of a blastocyst) begins with the 16- to 32-cell morula stage embryo. Following cycles of contraction and expansion, zonular tight junctions are formed between peripheral blastomeres resulting in a barrier that allows for the development of the blastocoel within the embryo. At the end of the cavitation the blastocoel comprises about 64-100 cells.
Green outlines trophoblast. Cells fit together tightly like paver stones, typical of epithelium. Image from Bell and Watson, PLoS ONE 8:e59528.
Proteins are made that assemble into these tight junctions, which are structures that hold the cells together. Other proteins form special pumps called aquaporins that pump fluid into the blastocoel cavity, the otherwise hollow center of the blastocyst. The blastocoel enlarges as cells degenerate in this area, a process of programmed cell death, until the embryo resembles a hollow sphere. It comprises a single layer of large flat cells on the periphery called the trophectoderm or trophoblast and an eccentric aggregate known as the inner cell mass (ICM).
Blastocyst with some trophectoderm labeled green. From Galat et al. Stem Cells and Development 18:1309, 2009. Published by Mary Ann Liebert, Inc., NY
The trophectoderm will develop into the placenta and associated membranes (together known as extraembryonic tissue) and is responsible for implantation, while the ICM will develop into the fetus. The pole of the blastocoel with the ICM is the embryonic pole while the other pole, is called the abembryonic pole. Thus there is an axis to the sphere, a “northern hemisphere” which is the embryonic pole and a “southern hemisphere” which is the abembryonic pole.
The blastocyst exhibits a high rate of metabolism, resulting in the process of the hatching and shedding of the zona pellucida (our version of an egg shell). The zona pellucida has to be removed before the embryo can attach to the uterine wall. This action includes an enlargement and a rhythmic undulating movement. Single large contractions of the blastocyst can result in nearly complete disappearance of the zona pellucida. Large contractions occur every 6-8 hours, and they are interspersed with smaller contractions every 20-100 minutes. Some contractions are slow (5-6 minutes), while others are relatively fast (15-20 seconds). At the time of hatching the blastocyst is no longer spherical but slightly ovoid and varies considerably in size (96-108 micrometers). At this point the blastocyst can contact the uterine epithelium for the attachment phase of implantation.
Blastocyst showing CDX2 expression in light blue (e.g. next to the yellow arrow). Image from Bell and Watson, PLoS ONE 8:e59528.
Gene expression is correlated with these steps. A gene called CDX2 [more on gene names here] is expressed in random cells at the earliest stages of the embryo before compaction. When the cells on the outside of the embryo become polarized (develop distinct differences at one end of the cell vs. the other end) then CDX2 expression becomes restricted to outside cells. Nanog expression starts out in random cells but is stopped by CDX2, therefore Nanog becomes restricted in its expression only appearing in cells that do not express CDX2, thus expression in the inner cells.
The same thing happens to GATA6 so the inside cells that do not express Nanog express GATA6. OCT4 is expressed in all embryonic cells early but is turned off by CDX2; therefore it is turned off in outer cells where CDX2 is turned on. So in the blastocyst the trophectoderm (which becomes the placenta) has CDX2, all of the cells of the inner cell mass (which become the fetus) express OCT4, some of these also express Nanog, while others of these express GATA6 resulting in distinct populations of cells within the inner cell mass.
So this is really incredible! At these very earliest of stages as the baby is just beginning to be formed critical steps that start us all off begin as activity of a key gene product (CDX2) that acts like a master switch in random cells. This is then refined by the geography of the cells (who is inside who is outside)! The switch then operates to establish a population of cells, the inner cell mass, that will form the fetus and has another switch (OCT4) set to on that makes those cells retain the ability to form all the tissues of our bodies. At the same time the first steps in that population of cells is taken to allow them to begin to differentiate (Nanog and GATA6). This critical pattern of development self organizes!
The inner cell mass is also where we get embryonic stem cells!
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