Lecture 4 and 5
November 2, 201312:23 AM
Talked aout how cells organize themselves structurally and spatially.
Now we talk about how they develop.
1. Morphogenesis: the generation of tissue shapes which forms the
2. Cell differentiation: (next lecture) the generation of different cell
morphogenesis types in different tissues. - we will be focusing on changes in gene
expression in which they change behavior and identity.
Morphogenesis involves a number of things
BIO230 Page 1 In early embryo there is cell proliferation so that you have
enough cells to start working with
Some of these cells becomes specialised, can also be viewed as
differentiation because one cell ebcomes different from
antoher, from another because of the different gene
expression. They all have the same genomes but the expression
So the cell starts behaving differently from its siblings. It might
feedback and afect proliferation: stop or increase cell
proliferation. Affects how they move , the cell interaction, etc.
then the cell can form different structures. this is
Additionally the cell specialization will also affect the function
of the cell. You can create a muscle vs a neuron. They will look
different and form different functions in the adult bodu
It will change how they ineract with each other and it also
affects how they move within the organism.
Morphogensis is not exactly separate from one antoher.
There is a wide number of model systems you can use to study
Gives the advantage of studying separate studies.
Like high reproduction.
One important aspect of this is that many of these are conserved
among model systems.
Nematode worm These developmental mechanisms are conserved across evolution. If
you have a system which is conserved among these systems then that
means that is important for development. There is a reason why its
conserved and used again and again.
Vertebrate models are close to humans and are closer models to
The close the model is to the us the closer we can apply them to human
BIO230 Page 2 Formation of the heart/ brain/ lungs can be thought of as having their
own development processes. / autonomous from one another.
Development processes keeps on happening in adults:
They doesn’t stop in embryogenesis.
Its key in adults for maintaining the tissues.
1. One is in the skin; the skin epithelium here: it’s a stratified
epithelium. it is multilayered. Cells on top of cells.
Beneath the stratified epithelium we have the extracellular matrix
(connective tissue) and ECM molecules, and single cells migrating in
Multiple layers provides protection from the Surrounding environment.
The environment is harsh and the top layer of the skin cells are dead
and it continually loses skin cells. Because we are losing skin cells we
need stem cells from the base of the tissue which is resupplying the
If we don’t have the continuous resupply of cells we are losing the skin
within two or three weeks. How quickly the skin cells are turning over.
We have a new layer every two or three weeks,
BIO230 Page 3 Another example:
The lumen of the gut also has a very harsh environment. The cells
exposed to this environment are also constantly lost.
The epithelium right here is a single (monolayer) epithelium sheet
which loops in and out forming a villi,
Up the villi is the lumen of the gut. On the other side is the ECM.
Typical arrangement of an epith. Sheet
Right at the tip there are epithelium loosing. They are dying. So there
should be resupply of them.
Right at the base of the villi is the crypt. At the base of the crypt there is
the individual group of cells which continually resupply tissues. These
are the stem cells which are continually making tissues to resupply.
If its stem cells are not there, You lose the lining of the gut in four
In a woman when she became pregnant her mammary glands undergo
new development processes. start with a simple epithelium. In
preparation for feeding the infant the epithelium tissues buds off the
alveoli . All the elvolie develops iff the tubes. the little circles. If we
blow one of them up, its an individual epithelium monolayer. (simple
epithlium, indivudla epithelium cells are shoen in pink, nuelci in darker
This sheet is going to pump milk into the lumen of the organ, then
themilk is going to pass the aveolai and into the larger epithliu tube to
feed the infant
Example of apical basal polarity and trafficking within the cell.
Individual cells are Making this milk fat droplets inside the cell, -->
trafficked to the apical domain --> fed to the baby
BIO230 Page 4 These developmental strategies are used again and again. In
embryogenesis, organogenesis, stem cell development and also in
We start off with a simple ball of cells called blastocysts.
We are looking at the mouse, the formation of the simple cells
The fertilized mouse egg, the haploid nucleus from the mother and the
haploid nucleus from the sperm --> nuclei will fuse to make the diploid
embryo-->the embryonic cell will divide a number of times --> there is a
clump of loose cells at first.
Then it will go through a process called compaction where the cells
gain cell -cell adhesion to one another --> and then it gains compaction
by cadherin molecules and cadherin is expressed which connects the
cells to each other
Then there is three main regions in the embryo --> an empty region in
the middle called the blastocoel , the outer epithelium called
trofactoerderm and inner cell mass : a group of cells in the outer
This inner cell mass gives rise to the mouse/embryo, trophectoderm
gives rise to the extra embryonic tissues which supports the growth of
the embryo, like the placenta.
From the fertilized cell you can make both the embryo and the
This inner cell mass then can make the mouse.
This is the mouse. The inner cell mass is just a clump of cells and haven't turned into a
BIO230 Page 5 The inner cell mass Is ONLY the embryo
There are major things that have to happen to turn into the mouse.
We know that there are types of cells outside and types of cells inside
our body. So we need internalization of cells.
Embryo is not a ball of cells, so elongation occurs.
There are three topics we are going to talk,
1. Gastrulation: defines three main germ layers to the embryo
Blastocysts: process of internalization of cells from blastocyst is called
gastrulation Creates three germ layers:
Ectoderm, endoderm, mesoderm.
Ectoderm of the sea urchin: found outside of the embryo.
Derives the Epidermis of the skin . The nervous system which is
derived from the epidermis
Endoderm: makes the digestive tract and organs which buds off the
Ecto is outside, endo is inside.
In between it’s the mesoderm: gives rise to muscles, cells of the
connective tissues, blood vessels.
We walked in through the skin to the lumen of the gut in last lectures
abdomen. Its similar in this too.
You start off with the blastocysts which is a hollow ball--> this hollow
ball is the entire embryo--> i(different from the mouse)if we flip back
ectoderm one slide it looks like a hollow ball. So the hollow ball is coming from an
inner cell mass which is coming from a more complicated way. Some
mesoderm cells starts to detach from indivudla cells from the outer layer of cells
and starts migrating inwards and start crawing inwards. The inward
endoderm bending starts to make the digestiv etract and passes inway through
BIO230 Page 6 Two main mechanisms to get cells inside the embryo:
This is one mechanism,
Where single cells separate from early outer epithelium.
You can see the outer epithelium here
Basal side will be facing the fibres, the connective tissue
The other cells, Because they are not lined up perfectly in the
Single cells separate epithelium, they are breaking off the individual cells and is appearing to
look as if they are migrating
basal metastasise into secondary sites.
Metastasis is extremely dangerous in cancer progression.
If we understand the epithelium methucl..transition we can stop the
this progression of cancer.
During development this is highly regulated and the embryo controls
which cell are allowed to undergo the local breakdown of tissues so
cells can migrate away, and also controls where these cells are going to
go in the embryo
BIO230 Page 7 This is highlighted here:
You can take a group of cells which you know is going through this
You can transplant them out of a quail and transplant them into a
chick. We go from a quail to a chick because. you do this because
these cells are not rejected by the chick because the organisms are
But there are quial proteins which are not found in the chick, we can
follow where do these cells go? Where do these unwanted cells go to?
As the wing develops you can get a cross section of the wing and see
that it specifically fomrs the muscle.
Where the intact epithelial sheets moves inside the embryo
No breakage, but only bending inwards
Nice tall columnar individual cells/ all are rectangular from side view.
Intact epithelium sheets At the apical domain, the actin and myosin that contract specifically at
the apical domain. it makes the top of the cell to move in. instead of
making a columnar it makes a triangle which initiates the
internalization of the whole group of epithelium cells. (one triangle next
to another triangle next to another triangle creates a bend)
Happens in the formation of the
neural tube - neurulation
As the apical ends become narrower,
Their upper surface
membranes becomes thicker
BIO230 Page 8 This drives the formation of the neural tube--> forming the spinal
In this it’s the ectoderm of the embryo. This is a frog embryo.
Ectoderm is going through apical constriction and forms the neural
tube --> tube is a cross section runs through the whole length of the
embryo forming the spinal cord and the brain.
Series of micrgraphs of the drosophila to make a
These cells are marked with indiviudal nuclei. Apical
constriction and inward bending of the tissue: cells are
going to move inside the embryo --> detach--> and
migrate around the nside.
Example on how a sheet can move inside an embryo.
In the last slide the cells were intact and didn’t move.
This cells dissocaite and migrate around
The ectoderm was talked about in the last slide. This slide mesoderm.
So different organisms uses different strategies to internalize. Like in
here. Not the same strategy for al tissues in all animals
BIO230 Page 9 This is highly regulates, cells marks with a nuclei are told to internalize.
Internalization is highly regulated by TF TWIST!. Cells that are marked
by nuclei are marks so only these cells are internalized. This is done by
Cells that expresses the Twist moves into the interior of the embryo
and forms the mesoderm. Others remains outside.
BIO230 Page 10 Example of neural tube formation:
Cross section of early frog embryo.
The neural tube is forming. At the same time the neural tube is forming,
the body of the embryo is elongating.
Shifting from a walnut to In the end it looks like a tad pole
How does it happen?
Through specific cell rearrangement.
The cells start to migrate to the midline (the green arrows). As they
migrate in they push the neighbors to the head and tail. This leads to
the extension of the body. So we have a convergent of cells to the
midline and extension along the anterior posterior axis.
This is a process called cell integration.
Put your fingers togetherand The four fingers are contacting each
other. You can see that its 4 rows of fingers high. Now indigiate youe
fingers, so Fingers are moving towards the mid line os you now
youhvae 8 rows fingers. This is regulated in the system so cells know
where to go.
Directionality : migration to the midline tells the cells where to go.
BIO230 Page 11 We have a convergent of cells to the midline and extention along the
anterior posterios access. This is called cell integration.
Migration is regulated so cells know where to go.
Another way to extend is by making more cells.
Ex: Root hair of plants
Root hair, They can extend very quickly, dive into the soil to look for
That’s because they have a zone of cell division on the tip of the root.
Upstream of this All the tissues are held together in the cell wall
within the cell so it’s a static structure. And there is cell division at
Only way the newly formed tissues can go is down. Preformed tissue is
holding it back. Can't go up because of all the cell walls. By Having
localized cell division you can force the growth downwards and force
the extension of the tissue.
There is also a zone of cell elongation as well as a zone of division. Cell
sape change occurs there. This is how plants regulate their structure.
They can orient their elongation but arranging the cellulose around
their cells and also turgor pressure
• Cell is divided --> elongated --> differentiated through the three
zones at the root tip
BIO230 Page 12 They can orient the elongation by orienting cellulose around the
cells and also turgor pressure. Water is critical for plant structure if
no water it flops over.
Plant needs to be inflated by water.
Now if you have cellulose fibres around a cell in a particular
orientation then they can direct the direction of inflation.
If you are holding a partially inflated balloon and inflate it, the
direction of the balloon is dependent on the direction you hold it.
B: the collagen fibres are holding back the extension of the cell in
that direction so the only way the cells can expand is that direction.
If you stack these cells on top of one another you are making a short
If you inflate a balloon the other way the balloon can go up or down.
So in C, water can only push up or down effectively. So the cells stack
on top on another forming a tall plant.
Emphasize: Changes in cell division and shape are critical for animals
Ex: gut - The zone of dividing stem cells leads to a zone of rapidly
dividing cells. Bsically you are have cell division happeing in one part of
the cell and below it there is the ECM. Above it is the open lumen. So
the Only place the cells can go is UP. They are forced to go up. Similar
to the plant root.
BIO230 Page 13 We need finer positioning of cells within the overall structure.
One mechainsm is cell sorting. Cell sorting was recognized in frog
embryo when the three germ layers were dissociated as single
cells and mized back together.
Mixture of cells randomly mixed together,
Second: somehow can sort out from one another.
There is some information in the cell which tells where and whom
it should interact with. This provides finer information on where it
should be in the embryo.
BIO230 Page 14 There are three differential cell cell adhesion/ cadherin expression. We
have different cadherin expression which is linked to cell sortin. We
talked that cadhernid interacted homophilically. E cadherin interacts
only with E . Vice versa. This is the homophilca bond between cells.
The key idea: the fact that cadherin interacts homophillically.
E with E. R with R.
If you look at the brain, there are distinct zones in the brain which
expresses e cahderin, r cadherin etc.
Now there is attraction between the cadherins when you look at the
brain you see that there are different zones in the cell which xpresses
cadherin 6 , E and Z.
When you look at the large zones of the brain we know there is a finer
position in the brain.
The brain is like a computer. How is its wiring setup?
Cells are in different places of the cell.the larger structure is called the
cell body. Where ever the nucleus is its called the cell body, out from
the cell body there are extremely long extensions.
there are axons and dendrites which wire up the body
Cell bodies are in specific places and the cell extensions go to specific
places in the brain.
First look how the cells are positioned and then how the extensions are
What it forms is the neural tube
BIO230 Page 15 Formation of the brain:
Forms from the neural tube. The formation if the neural tube is through
invagination. We have a tube of Epithelial cells running from the top to
the bottom. Top forms the brain. The bottom forms the spinal cord.
Neural tube doesn’t have anything extended from it.
Brain has to form more cells to make the neurons needed in the brain.
Neurons start to divide. (progenitor cells for neurons) The daughters of
the progenitor the cells associate with radio glial cells--> they crawl up
the radial glial cells and occupy the zonal tissue of the radial glial-->.
Then radial glial extends a little bit further --> when the next neurons
are born -->. The next neurons walks even further out towards the
extremities of the made --> so it continues. Making third, fourth layer
of brain tissue.
These are called radial glial cells.
If we look at the brain, The radial glial are extendig in a radial
orientation. Like spokes on a wheel. You start off with a cell like this
and then walk to the first, second third layers.
This is how the cerebra cortex the layers of the brain Is made of.
This is how the cell bodies are made. Only the first step. We need to
wire the cell now.
If we know that these wirings have to go from cell body to cell body.
Where should the wirings be.
The axon is doing all the migrations using a specific structure called
growth corn which is at the tip.
This growth corn moves via actin based protrusions.
The growth cone is like the immune cell that was chasing the
bacterium( you can think like that). Same process as the front of the
it can move and push the cell forward. Difference is that the immune
cell moves the whole body. But in this the cell body stays in place so
instead you have a long extension in between.
This is extremely precise and can be reproduced In the body
BIO230 Page 16 You can get a dye and observe the zone of projections from one part of
the brain. From the eye to the brain. Get a tadpole and inject one dye
and can see the axon going from one part of the brain to the opposite
Somehow the neurons knows how to migrate from the brain to the eye.
There are so many neurons its complicated to understand the path.
There are so many neurons are made.
So instead of looking at the process at the brain, we can look at the
process further down the neural tube and ask the behavior of neurons
down the neural tube. Below slide.
Dyes go to opposite sides.
You can look at the procedure further down the neural tube and ask
the behavior of neuraons down the neural tube. From the neural tube
to the brain.
You can look at the axon path finding from the neural tube to the brain.
Basically around the neural tube Neurons been born all through out the
tissuse . Then they send axons ,first down to the midline of the floor
plate. That means one side of the tube, they all send axons to one side
of the tube and they all migrate it towards the brain.
All the axons forming the spinal cord are going to go towards the brain.
This is the growth corn at the tip of the cell so it has to make a couple
of decision. At first has it to find the midline --> then the brain.
It is not complicated as in the brain, but still reamarkable.
BIO230 Page 17 This is the tip of the axon. We are looking at the growth cone here.
Right along the mid line, center of the tube, of the group the first
step is attraction to the midline --> occurs through a process similar
to the immune cell chasing after the bacterium
Attractant is secretes a protein along the midline and forms a
gradient( like the bacterium secreting small moelcule) --> cell
receives the signal---> recognizes gradient -->orients the actin
protrusion machinery in the midline --> migrates ti the midline
Just like in the immune cell
Diffence is that if the immune cell captures the bacterium and its job
But in this the growth corn has to turn and migrate to the brain after
it reaches the first step.
How does that happen?