BS373:Principles of
Development
,LECTURE 1: MODEL ORGANISMS
Principles of Development
- Each of us has developed from a single eggs. These here are examples of many organisms as they
go through development
- One of the main questions in developmental biology, is how does this one cell coordinate the stages
of divisions and communication between other cells in order to result in a fully developed organism.
- How is the developmental programming coded into DNA?
- One of the reasons of studying development is due to its medical importance, as there are many
abnormalities that can be due to issues during embryonic development.There can be mid ones, such
as people with extra fingers, or they can be major developmental defects that account for 70% of
neonatal deaths and foetal lethality.
- Another reason why study development, is that there are some organisms
that are able to regenerate and they seem to recapitulate some of the
processes occurring during development. This is very interesting for humans,
as most of organs we can’t regenerate anymore. So by finding out mechanisms
that are working in other organisms, we might be able to apply similar
principles for human organisms.
- The Mexican salamander can regenerate limbs and organs like the pancreas
and can help identify key mechanisms for cell regeneration.
Common model systems used in developmental biology
- These developmental mechanisms of the animals
used in the lab for embryology and developmental
biology, are very similar to each other, even thought
the animal might seem very different to us.
- We can illustrate how organisms are different in
development
Apoptosis is highly conserved in evolution
- The conservation of development, meaning that the
common features in development from different organisms
can be very useful. If we learn how they are working in
mouse for example we can apply this knowledge in other
organisms, such as humans.
- There are features that are conserved among very distantly
related animals.
- This is the development of the fins. At the top we see the
developing limb of a mouse. At the beginning we cannot
distinguish the fingers. As development progresses, we can
see the light-green cell layer that is dying, through programmed cells death also known as apoptosis.
Eventually all cells between the fingers go through apoptosis. However in whales, even though their
bone structure is very similar to humans, they have funs and so there is lack of apoptosis between the
fingers.
, Apoptosis genes are conserved in sequence and function
- It turns out that this genetic programme that triggers cell death is highly
conserved.
- So the genes that control cell death of these organisms have been
found in almost all animals.
- Apoptosis was initially identified in C.elegans, which is a nematode. In
that animal it is very easy to find which genes are involved in that
process.
- It was found that in C.elegans, EGL-1, CED-9, CED-4 and CED-3, are
involved in apoptosis. The same genes were found in other animals and
mammals. This knowledge for genetic program that causes cell death is
of high interest because if you can manipulate those genes, you can
activate cells that we would want to die, such as cancer cells, or we
could prevent programmed cell death from happening, such as cells
dying in neurodegenerative diseases.
Conservation of mechanisms across long evolutionary distances
- The conservation of mechanisms such as the development of the eye
has been studied in mammals and drosophila.
- It was found that the same gene controls the development of the eye in
drosophila and mice.
Mutant for Pax6 has similar phenotype
- We can see here wild type drosophila that the eye is intact. In the right panel we
can see a drosophila mutant for the gene Pax6 and this mutant doesn’t have an
eye
- We can see a newborn mouse that the left one has an eye. The mutant for Pax6
doesn’t have an eye.
Choosing model systems according to question of investigation
, Criteria for choosing models
- One of the criteria to choose which model system is
better for my research is generation of the lifespan of
the organism.
- For example the chicken is good for transplantation
of tissues from one place to another in the embryo, it
has a very long generation time. So the chicken has an
egg development and until it hatches it needs 20 days,
which is generally quick. But then for the embryo to
become an adult it needs 10 months. So to see the
next generation, you need to wait for around a year.
- For the mouse its development is 18-20 days long.
The mouse becomes an adult after 5-6 week. So its
generation time is much shorter than the chicken’s and therefore it is better for genetic studies where
you need to see the next generation.
- Xenopus (frog species) has a very long generation time. The development of the embryo is short.
From the egg until the tadpole it takes 2 days. After that it takes a long time for the tadpole to undergo
metamorphosis and become an adult and for the mature adult to become reproductively active. So it is
not very good for genetic studies.
- Zebrafish is great for genetics. It has a short embryonic development, as it takes only 2 days to hatch
from the egg.Then it becomes an adult after 3 months. So it is one of the vertebrates with the shortest
generation time.
- For the invertebrates studies, Drosophila is a great model. It goes from an embryo and undergoes
metamorphosis within 24 hours and then it becomes an adult after 10 days after hatching from the egg.
- C.elegans needs around 18 hours to go from an egg to the 1st larvae stage and then it needs 2-3
days to become an adult and then it starts reproducing right away. The generation time is extremely
short.
- All these organisms are needed for different reasons and they are all very helpful for research. Their
generation time is relatively short, besides the chicken and the. frog.
- Criteria for choosing models:
1. For keeping these organisms we need different infrastructure. For the mice we can only keep 3-4
mice in the sam cage. So if we need many mice, there is a great amount of cases required.
2. For zebrafish we need tanks that have purified water that goes through the whole aquarium and this
means some expensive mechanism is required.
3. For C.elegans, thousands of them can be kept in an agar plate, so it is very easy and cheap to be
kept.
4. For the use of mammals in labs, veterinarians are required, which means that this is an extra cost
that needs to be included. This is 1$ a day for each pound to be kept in the lab and checked by a vet.
Universality of animal models
- Although the criteria for choosing model systems for studying
developmental biology varies according to how important and
useful they are to investigate and come into conclusions about
organisms and the knowledge we can gain from these organisms
for humans, we need to be careful. Many of these organisms have
unique features that are not found in other organisms. And this
means that they can be less useful for some specific questions, as
these unique features cannot be generalised to other organisms.
- This picture is the example of Drosophila. It is a common fruit
flies that is a very popular model system, as many cellular mechanisms that occur during embryonic
development are very similar, if not the same to many other organisms including humans. However, the
first cell division in Drosophila is very different from other organisms. That is because the first cell has
one nucleus and everything else is yolk and RNA. This cell doesn’t divide normally like any other cell but
