1) Early mammalian embryonic development involves cleavage divisions that result in a solid ball of cells called a morula. 2) The morula develops into a blastocyst containing an inner cell mass and outer trophoblast layer. 3) Around 7-10 days, the blastocyst implants into the uterine wall and the trophoblast penetrates the lining, forming finger-like villi that will become the placenta. Extra-embryonic tissues including the amnion, yolk sac, and allantois develop to support the growth of the embryo.

1. Early development of the
embryo
The aim of this lecture is to
consider how the fertilised zygote
begins to develop.

2. • A great deal of the investigation of embryonic development has been
done on animals such as amphibians (frogs and the clawed toad,
Xenopus laevis ), echinoderms (sea urchins) and insects (fruit fly,
Drosophila melanogaster ) and birds.
• Although many of the concepts and even details of the process are
similar in humans and other mammals there are significant differences.
• Frog eggs are about 2000x the size of a mammalian egg and bird’s
eggs are even larger. The size is needed in these eggs since the embryo
develops externally and independently so the egg must contain all the
materials needed for full development of fully formed offspring.
• Mammalian eggs can be much smaller as they develop internally and
are nourished via a placenta for most of the developing period.

3. • However it does mean that mammalian eggs must develop extra
structures to allow connection to the maternal uterus which are only
used as life support systems and play no part in the structure of the
embryo. These extra-embryonic structures are discarded at birth..
• In this course we shall concentrate on the mammalian development
with only references and comparisons to development in other species.

4. Cleavage and morula
formation
• The two pronuclei (maternal and paternal) remain separate until the
first mitotic division and then the chromosomes merge as they attach
to the spindle fibres formed from the sperm centriole.
• This first division is much later in development than equivalent in
amphibia and occurs at about 36 hours after fertilisation. The divisions
of the early zygote are referred to as cleavage divisions to differentiate
them from normal cell division.

5. • In frogs etc the divisions follow rapidly with nearly complete loss of
the G1 and G2 phases and so the daughter cells become progressively
smaller as they divide.
• Mammalian development is slower but retains the decrease in size of
the cell and the cells are retained within the limits of the zona
pellucida for the first few divisions.

6. Zona pellucida
2 Cell Stage
36 hours

7. • The cleavage in mammals is even with cells all being equal in size and
entirely equivalent (holoblastic cleavage ) unlike frogs and birds
( which show uneven cleavage or meroblastic cleavage).
• It is possible to separate the cells at this stage and each cell is capable
of developing into a full normal embryo and this is how identical twins
arise (monozygotic twins ie arising from a single zygote).
• In animals up to eight identical octuplets have been formed
experimentally.
• It is also considered reasonably safe to remove a single cell at this
stage for diagnosis. The cell can be used to detect if the embryo is
carrying a gene for a serious genetic disease such as
adrenoleukodystrophy or Huntington’s disease. This is still an
experimental technique rather than a routine procedure.

9. • The cells at the eight cell stage undergo a significant change called
compaction . This involves not only a closer packing of the cells but
also the production of new membrane proteins of the cadherin group
which keep the cells linked together.
• The sixteen cell stage resembles a berry (blackberry, raspberry or
mulberry) and is termed a morula from the Latin name for mulberry.
This occurs at around 3 days (72 hours) after fertilisation.
• Up to this stage all the cells divide at approximately the same time
(synchronous division) but after this stage the divisions become less co-
ordinated and gradually become asynchronous.

10. Blastocyst formation
• The next major feature is the development of a hollow cavity called the
blastocoel and this signals a significant change in the cells forming the
embryo.
• A layer of cells around the blastocoel is called the trophoblast ( or
trophectoderm)and this layer will be involved in the implantation of
the blastocyst into the uterus but play no part in the structure of the
embryo. The whole of the embryo proper comes from the inner cell
mass.

11. • It is possible to experimentally introduce cells from a different
embryo into the blastocoel and they will mix with cells already present
and will help form all parts of the final embryo showing that at this
stage the cells are all equivalent (multipotent) rather than being
dedicated to forming one particular structure.
• An animal which has a mixture of different cells like this is termed a
chimera after a mythical Greek monster which had the head of a lion,
the tail of a serpent and the body of a goat).

19. Implantation
• It is at around this blastocyst stage ( 7-10 days) that implantation
occurs.
• The zona pellucida is lost and the trophoblast cells can contact directly
with the uterine lining and the blastocyst secretes enzymes which
break down the lining allowing the trophoblast to penetrate into the
uterine lining .
• The blastocyst is surrounded by maternal blood from eroded vessels
and the trophoblast layer thickens and produces finger shaped
processes (villi) and this region will later develop into the placenta.

21. Formation of Extra-embryonic
sacs and mesoderm
• The trophoblast continues to spread and will become the chorion with
extensive villi.
• Whilst implantation is occurring the inner cell mass reorganises to
form a cavity called the amniotic cavity lined by epiblast cells.
• The amnion enlarges during development and completely surrounds
the embryo as a fluid filled amniotic cavity which acts as a major
mechanical buffer for the embryo and foetus.
• This leaves a flat disc of cells from which the embryo will form.

23. • The lower layer of the cell in this disc forms the hypoblast and this
proliferates and migrates to form a layer surrounding a cavity referred
to as the yolk sac
• This name arises by analogy with the yolk sac in other animals but in
mammals this cavity never contains yolk.
• The yolk sac is an extra-embryonic structure but does act as the main
source of blood cells for the early embryo though this later transfers
into the main embryo.
• The epiblast forms the ectoderm of the embryo from which the
epidermis and the nervous system arise while the hypoblast forms the
endoderm from which the lining of the intestinal canal and its
derivative structures.

25. • The spaces between the amniotic cavity and the trophoblast and the
yolk sac and the trophoblast become filled with cells which are
believed to migrate from the epiblast layer. This middle layer is called
the extra-embryonic mesoderm.
• The embryonic mesoderm develops from the endoderm by folding
inwards and downwards of a furrow in the ectoderm ( this is
equivalent to gastrulation in the frog where the infolding also forms
the intestine and the furrow in the ectoderm is the equivalent of an
extended blastopore).
• The mesoderm later forms all the muscles and connective tissues in the
body.

28. • One final membrane develops from the endoderm of the early gut and
this is the allantois.
• In birds this remains as a sac into which the waste products (eg uric
acid) and presses against the shell where the lining acts as a respiratory
organ for the developing chick.
• The allantois in mammals becomes part of the umbilical cord linking
the embryo to the placenta.