Lecture 14 p. 83 – 93
Cleavage is the first event that occurs after fertilization. It converts the unicellular egg into a
There are 4 central developmental processes that occur in human embryogenesis:
1. Cell Division (Cleavage): involves initial cleavage followed by regular mitotic cell divisions.
2. Cell Differentiation: Formation of different, specialized cell types.
3. Morphogenesis: the generation of shape; results in embryonic organization and development of
the pattern and polarity of organs and tissues. Cell differentiation is one component of
morphogenesis. Cell differentiation and morphogenesis are not synonymous.
4. Growth: Increases the size of a cell, tissue, organ or organism.
Functions and events of cleavage:
Initial division of zygote to multicellular embryo.
Mitotic divisions maintain the diploid (2N) complement of the genome.
Rapid cell division, no growth
Blastomeres get smaller with each division
Holoblastic cleavage; complete separation of blastomeres
Cleavage has a shortened cell cycle. The normal cell cycle has four phases; growth phase 1, (G1), DNA
Synthesis (S), growth phase 2 (G2) and mitosis (M). There is no G1 and G2 phase during cleavage and
hence cleavage cells become smaller in size. All resulting blastomeres will be genetically identical. Since
each blastomere has a diploid nucleus, the amount of nuclear DNA in the embryo also doubles. The zygote is surrounded by the zona pellucida which is
separated from the cell itself by the perivitelline space.
The first cleavage/ division gives a two-celled embryo i.e. two
blastomeres. Now the embryo has double the DNA content of
the zygote and it has made membrane to surround both cells.
No growth has occurred so the two blastomeres together are
approximate equal to the size of the original zygote.
After 2 cleavage the embryo has four cells, and four times the DNA content of the zygote. Membrane
now surrounds all four cells and the four blastomeres together = size of original zygote.
After third cleavage the embryo has 8 cells and 8 times the DNA content of the zygote. Membrane
surrounds the eight cells and still no growth so the eight blastomeres = the size of the orginial zygote.
Then embryo undergoes compaction leading to the 16
After compaction fluid appears between the cells after
the morula stage resulting in the early blastocyst. The
fluid accumulates in an increasingly larger cavity called
Compaction occurs when cells adhere together more
tightly at the 8-cell stage. The embryo becomes more
compact, but the cells remain separate from each other.
E-cadherin causes the cells to adhere more tightly
E-cadherin is a cell adhesion molecule that is involved in
calcium-dependent binding. N-cadherin, involves the
adhesion of nerve cells. E – cadherins mediate epithelial cell adhesion. P-cadherins localize the placenta.
E-cadherin molecules from one blastomere homophilically associate with cadherin molecules on
adjacent blastomeres leading to their tight adhesion. E-cadherin, present during cleavage, will be
replaced by N-cadherin when multicellular tissue formation begins (gastrulation).
The presence of E-cadherin can be detected at the surface of cells in compacted embryos using
immunofluorescence microscopy. If cells are treated with anti-cadherin at the time of compaction, they
do not undergo compaction. Anti-cadherin binds to other cadherin molecules.
Epithin is a mammalian transmembrane serine protease that has been found to be associated with E-
cadherin in a diversity of tissues. Epithin and e-cadherin co-localize at the 8-cell and morula stages. Cavitation is the appearance of fluid between blastomeres in the embryo as cell numbers increase. It
begins approximately four days after fertilization and leads to the formation of the blastocoele.
Human eggs hatch prior to
During hatching the embryo
breaks through the zona
pellucida due to proteases
that have been secreted by
the blastocyst. Inability to
hatch causes infertility and it
could be due to the presence
of an altered zona pellucida or absence of proteases for zona pellucida digestion.Assisted hatching is
done in vitro during ART procedures. In mutant mouse embryos lacking ZP1 protein, the zona pellucida
is weak and the embryos hatch prematurely which may lead to ectopic pregnancy.
Lecture 15 p. 94 – 101
Implantation of the embryo occurs approximately 6 – 7 days after fertilization. During implantation, the
embryo will bind to the uterine epithelium then penetrate it transforming the embryo into a fetus.
LECTURE 17 & 18
Chapter 10 p. 102 - 109 Gastrulation is the first phase of development in the fetus. It defines the primary germ layers (ectoderm,
mesoderm and endoderm) and sets up new cellular and tissue relationships essential for development.
Gastrulation will occur in the epiblast.
Delamination occurs before gastrulation. It separates the inner cell mass , ICM, into the epiblast and
hypoblast just before implantation and gastrulation. After cleavage, morphogenic movements will
reorganize the embryo into distinct layers.
The epiblast becomes a 2-
layered (bilaminate) disc of
cells that will form the
embryo proper. The flatter
layer of hypoblast cells lies
below the epiblast will
continue to the yolk sac.
Gastrulation will convert the bliaminate epiblast into the three primary embryonic germ layers:
1. Ectoderm – outside; surrounds the other germ layers
2. Mesoderm – middle; lays between the ectoderm and endoderm
3. Endoderm – inside; lies at the most interior of the embryo
No experimental work is being done on human gastrulation because is not ethical or legal. This makes it
difficult to get specific stages or to define when and how specific events occur.
Recently researchers have been able to fluorescently label cells and follow their movement using
confocal microscopy to obtain sharper resolution of stained material and its precise location in a time-
dependent manner. Confocal microscopy is a special laser-based microscopy which allows researchers
to take optical sections through tissues to construct 3D images. At the start of gastrulation the human epiblast is bilaminate. Initially cells move along the surface and
once at the centre line (primitive streak) they enter the embryo at this point. The cells then turn the
corner and move internally. As they enter the moving surface cells first pile up to form a bump known as
the primitive node. It is called the Hensen’s node in other animals. The pile up occurs because the cells
move along the top faster than they can separate off and move internally.
The cells that enter through the primitive node will become the notochord.