Development
1
Slide 1
Two linked themes for today:
- Single-cell and multicellular
organisms, and the advantages in
being multicellular
development: how individual
human life begins (as a single cell);
how our development from single
cell to fetus parallels some of the
changes in evolution; similarities
between embryos or fetuses of all
vertebrate species; how organ
systems develop
Slide 2 - Scale
How many bacteria can sit on the
point of a pin? Here is an electron
micrograph of a standard domestic
pin at several different
magnifications. Bacteria are a
fraction of a micrometre in length
(a micrometre is a thousandth of a
millimetre). Your cells are
somewhat larger, with the largest
being just visible with the naked
eye.
Slide 3
Introducing multicellular life. The
main advantage to an organism in
being multicellular is that it can
control the environment of its cells,
because the environment of each
cell is the inside of the animal.
This is the concept of the “internal
environment” as first noted by
Claude Bernard; multicellular
organisms keep their internal
environment constant, as far as
possible. They do this by
specialisation of cell functions.
2
Slide 4
How did multicellular life
originate? Which were the first
multicellular organisms to
specialise their cell functions? The
simplest ones that survive today
are sponges, which have several
specialised types of cells including
structural cells and choanocytes,
which have beating cilia which
move water into the interior of the
sponge so that the sponge can draw
nutrients from the water.
Slide 5
Wilson’s 1907 experiment referred to here
consisted of passing a sponge through a
sieve to separate it into single cells. When
this was done, the cells spontaneously reassembled into a new sponge. In doing
this, they first went through a stage in
which they were no longer specialised
(de-differentiation). Each cell in a sponge
is able to re-create a whole sponge, i.e.
they are all germ cells. In contrast, most of
our body cells (somatic cells) have
irreversibly differentiated into their
specialised types. Only a few cells in our
body have the potential to create a new
person: these are our germ cells, either
sperm or egg cells.
Slide 6
Differentiation in our bodies produces
many different cell types and these are
organised on many levels. Cell types (2)
are organised into tissues (3), and several
tissues make up each organ (4). Organs
assemble into systems (5), each with a
particular role in maintaining the
constancy of the internal environment.
The systems level of organisation is the
most useful for our understanding of
physiology. It is one level below the
whole person (6).
3
Slide 7
Developmental biology is one of the most
exciting and productive fields in modern
biology. It concerns itself with how a
single-celled embryo develops into an
adult. This is the story of differentiation,
how cells change from undifferentiated
embryonic stem cells into the cell types
characteristic of each tissue and organ
system.
Much of this work is being done in
organisms that are much simpler than we
are. These “model organisms” include
simple vertebrates and invertebrates. One
might wonder what relevance these have
to humans: humans and mice are after all
quite easy to tell apart.
Slide 8
However, at the early embryo stage, all
vertebrates look more or less alike. This
observation, first made by Haeckel (see
picture), indicates that many
developmental pathways are shared. Some
are shared in surprising ways. For
instance, a major gene that controls eye
formation in Drosophila is very similar to
a gene with similar function in humans:
this is surprising, not only because our
eyes are so different and our common
ancestor lived at least 500 million years
ago, but even more so because that
ancestor probably didn’t have eyes! (the
answer to this surprising problem might
be that the gene originally controlled a
rudimentary light-sensitive structure that
evolved to become the very different eyes
of insects and mammals)
Slide 9
The two questions each cell has to “ask
itself” are:
•where am I in the organism? and
•what should I do now that I am here?
Developmental biologists are finding the
signals that answer these two questions.
In general terms:
•location is specified by gradients, often
of some diffusible substance (e.g. more
retinoic acid is found in proximal than in
distal regions)
•cells respond by switching on and off the
appropriate genes corresponding to the
location they are in.
4
Slide 10
The most important theme of this lecture
is your own development: how does a
human baby form from the initial
components, an egg cell and a a sperm
cell?
The first step is fertilisation. One sperm
enters the egg; at that moment a reaction
of the egg (see Seeley if you want the
details) prevents any other sperm from
entering. The sperm and egg nuclei are the
male and female pronuclei and these fuse
to become the nucleus of the fertilised
egg.
Slides 11/12
Expanding on slide 10:
The male and female pronuclei each
contain 23 chromosomes. including an X
(female pronucleus) and either an X or a
Y (male pronucleus). The nucleus, after
fusion, thus contains 46 chromosomes in
23 pairs; one pair is either XX (the fetus
will develop female) or XY (the fetus will
develop male).
5
Slide 13
After fertilisation, the egg divides; each
division takes about a day. The slide
shows embryos at the one, two, four and
eight-cell stage.
Slide 14
The processes shown in the previous
slides happen as the egg makes its journey
from the ovary towards the uterus.
Fertilisation happens towards the top end
of the Fallopian tube. The embryo divides
on its way down the Fallopian tube, and
implants (see slide 20) when it has already
divided several times
Slide 15
Implantation is an active burrowing of the
embryo into the lining of the womb (the
endometrium). Nutrients are absorbed in a
way that does not differ greatly from the
nutrition of a single-celled organism. This
is the stage of trophoblastic nutrition
which lasts for about 10-12 weeks.
6
Slide 16
Introduces the next major stage in
embryonic development, which is in many
ways the most important: the point where
the embryo becomes larger and develops
recognisable structures which will become
its organ systems. It is no longer feasible
to get nutrition by simple diffusion and
here the circulation becomes essential.
The embryo thus makes the transition
from a relatively undifferentiated group of
cells, surviving by diffusion, into a
multicellular organism made up of
specialised systems working together to
ensure the survival of the whole.
Slide 17
The formation of the embryonic disk at
this time immediately precedes the
development of the first structures. The
disk divides two fluid compartments: the
yolk sac and the amniotic sac. These
names are important, especially the latter:
sampling of amniotic fluid
(amniocentesis) is one of the approaches
used in pre-natal diagnosis of inherited
disease.
7
Slide 18
One of the first recognisable structures is
the primitive streak. This runs across the
embryonic disk. It will become the
nervous system (see following slides).
Slide 19
The primitive streak becomes the neural
tube, by forming a fold then joining the
edges of the fold. The tube closes over
first in the middle then at the two ends.
Note that closure is at an advanced stage
20 days after fertilisation, one of the
earliest processes in development.
Slide 20
Sometimes the closure is not complete at
the distal end, and then spina bifida
results.
8
Slide 21
The digestive system also forms as a fold
which becomes a tube. The tube is closed
somewhat later than the neural tube, by
about 30 days.
Slide 22
The face develops later still. Note the
structures that must join, and where they
join. Failure to join properly causes cleft
lip or cleft palate, either of which will
cause speech problems.
Slide 23
Summary of the phases of development.
Note that the nervous system begins to
develop before the others and continues to
develop longer than any other system.
An important message here concerns the
effects of teratogens in the environment.
In the first two weeks, the embryo is
highly vulnerable and likely to die as a
result of exposure to any toxic chemical.
However the mother may not be aware
she is pregnant at that stage. The period of
greatest practical danger in terms of
teratogen exposure is from 2-12 weeks,
because that is when the major organ
systems are developing. Exposure in this
period may not kill the embryo, but may
well cause malformation in one or other
organ system (or limb malformation).
Later in pregnancy, the fetus is gradually
less and less vulnerable.
9
Slide 24
As the embryo develops, trophoblastic
nutrition is no longer adequate to supply
its needs. At about 10-12 weeks the
placenta takes over nutrition.
Slide 25
A reminder of slide 21 on implantation.
The structures that will form the placenta
are already in place during trophoblastic
nutrition (see also next slide)
Slide 26
Early stages in placenta formation.
Maternal blood vessels approach the
trophoblast, while embryonic blood
vessels are also forming and approaching
the interface with the mother. The
syncytiotrophoblast is the barrier, an
acellular layer which is also not antigenic
i.e. it doesn’t produce an immune reaction
in the mother. This barrier remains in the
placenta.
10
Slide 27
Fully formed placenta. Chorionic villi
carrying fetal blood push into the placenta
and are surrounded by maternal blood; the
syncytiotrophoblast is still present and still
forms the effective barrier between
mother and fetus. The chorionic villi
contain fetal blood vessels which pick up
nutrients and oxygen from the mother into
the fetal blood, and release waste products
from the fetal blood into the mother’s
circulation. The placenta is connected to
the fetus by the umbilical cord, which
contains fetal blood.
Slide 28
Formation of the heart. Clearly there has
to be a pump for the fetal circulation,
developing at about the same time as the
placenta. Initially the pump is a simple
thickening of the muscle around the aorta
(20 days) but shortly after that the
recognisable shape of the heart is present
(35 days). Importantly, at that stage, there
is no division between the two sides.
Before birth, the ventricular septum closes
to complete the separation between the
two ventricles. If this does not happen, the
resulting ventricular septal defect (“hole
in the heart” will cause disability if not
corrected. Surgical correction of
ventricular septal defect is now a wellestablished procedure. At birth, there is
still a functional connection between the
left and right atria (the foramen ovale; see
later).
Slide 29
Stimuli for birth come to a large extent
from the fetus itself: stress caused by lack
of space is an important factor. This stress
is increased by the rhythmic contractions
of the uterus, and cervical dilatation
caused by pressure of the fetus’s head
provides an additional stimulus increasing
uterine contractions.
11
Slide 30
The circulation changes profoundly
immediately after birth. The changes are
not obvious on this diagram from Seeley
(see the red boxes; before birth on the left,
after birth on the right). The lower slides
from another textbook show the changes
more clearly.
Slides 31 and 32
Before birth (31) and after (32).
Before birth, blood flows from right
atrium to left atrium through the foramen
ovale, and bypasses the lungs through the
ductus arteriosus. The lungs are collapsed
and full of amniotic fluid. The numbers
represent the percentage of blood that
flows through each pathway. Note the
small amount going into the right atrium,
and the small fraction of that which goes
into the lungs. Most of the blood flows
around the systemic circulation and
especially the placenta.
After birth, the placenta is no longer
present, and the two connecting pathways
(foramen ovale and ductus arteriosus)
close up. Now, all the blood entering the
right atrium flows into the right ventricle,
and none of it into the left atrium. All the
blood coming out of the right ventricle
now flows into the lungs. The right and
left half of the circulation are now
completely separate and blood flows
through one then the other.
See also next slide (taken from lecture 6).
Lecture 6 will have more on the
circulation.
12
Slide 33
Adult layout of the circulation. Note that
blood flows sequentially through the four
regions shown.
Slide 34
Corresponding to the major change in the
circulation, with blood flowing through
the lungs for the first time, we also have
the first breath: air enters the lungs for the
first time. The force required to get this air
in is enormous, far greater than any other
breath of our lives. This is because the
lungs are filled with fluid; introducing air
into them produces a surface (air/fluid
interface), and we have to pull against
surface tension to get air in. Note the great
suction that must be applied (-40 mmHg)
before the lungs even begin to expand.
Slide 35
Health of newborns is assessed using the
Apgar score. Named after Virginia Apgar
who introduced it, but her name is also a
useful mnemonic for the five aspects of
newborn health that are assessed. You can
find more on the Apgar score in the Best
& Bee textbook as well as in Seeley. It’s
important to have a clear idea of what is
measured and why it tells us about the
baby’s health. In brief, the measures either
tell us about the adequacy of oxygen
supply (appearance/pulse/respiration) or
about nervous system function
(grimace/activity).
13
Slide 36
Definition of prematurity. Prematurity has
many consequences, and the earlier a
child is born, the more serious the
problems are likely to be. The problems
are caused by immaturity of multiple
organs.
The most serious and life-threstening
consequence of moderate degrees of
prematurity is respiratory distress
syndrome. This will be explained further
once I’ve explained about the respiratory
system in a couple of weeks.
Suggested reading
The Boyd & Bee suggestion is intended if
you want to read more deeply into early
development. It is a very nice, readable
book that contributed a number of the
slides used today, but the essential
material is already in the Seeley series
textbooks.