What we talked about last time was formation of different types of
cells in the embryo, different positions, different
shapes. Am I on? And we talked about one of the
overriding principles of all of this being the control of gene expression.
I'll explore this a little more with a couple of slides in a moment.
Let me just write some points. So we talked about the control of gene
expression as being an overriding principle of how cells
types are formed. We talked about the fact that cell
types were formed in a stepwise fashion. And different parts of the
embryo indeed in a stepwise fashion. Not all at once. And we talked
about a combinatorial code --
-- of regulators that, together, specify different types of
cells. So here we are to remind you talking
about cell type in the formation module stepping through our board of
life. And here are a couple of slides to remind you what we talked
about in last lecture to bring you up to speed. You should look at the
PowerPoint on the Web if you have not already. Cell type is defined
by the proteins a particular cell makes.
For example, red blood cells carry oxygen around the body because they
make globin which is able to carry oxygen. The set of proteins that
are made are defined by which genes in a cell are active,
or expressed is the term you should know. And, therefore,
which genes are active, also called the control of gene
expression, controls which cell type forms.
This triad is essential for you to understand what we're going to be
talking about now and really for the rest of the course.
So you should really get it. If you don't see me, go back and
look at the previous lecture. And this lecture is going to also
reinforce this triad. I pointed out last time that gene
expression can be controlled at many levels.
In fact, at any point from transcription,
even from replication actually of the DNA through transcription,
splicing, translation, export of the RNA to the cytoplasm,
I haven't written up here, messenger RNA stability, protein
modification, protein export. Any of these steps is along the way
to getting the final gene product. And any of these steps can be
controlled to allow the readout of the final gene product or not.
I told you that along the way to becoming the final type of cell that
a cell is going to become, it goes through a couple of steps.
Or it can go through many steps, and we'll talk about that
extensively today. Cells begin as uncommitted or naive.
They don't know what they're going to become. They then become
committed or determined to a particular fate,
a position or a structure, but they may not look very different
from that first set of uncommitted cells.
And then they go on eventually to form so-called differentiated cells
or the final cell type which has the function of that particular cell
type. And so the point is if there is a stepwise formation of the final
cell type. And that final cell type is directed through the action of
regulatory factors that we termed inducers or determinants.
There is nothing magic about these. Inducers referred to factors that
were involved in cell-cell signaling. Determinants referred to regulatory
factors that acted within a cell and were inherited by it.
You shouldn't be trying to write all this down now actually because
this is really review. And if you weren't at the last
lecture, try to get some of it to wash over you and then go back and
make sure you really know this stuff.
And then as the differentiated cells form there is activation of a set of
genes called differentiation genes which are the things that carry out
the final cell function, the globin protein in red blood
cells, the neurofilaments and neurotransmitters in neurons and so
on. And we'll talk about this again as we go through today.
OK. So this is not unrelated to what we are going to
talk about today. Because what I want to do today is
to explore with you how you get a particular kind of cell.
And I want to use that exploration to underline some of the principles
that I haven't yet covered as to how cell type is determined in the
embryo. And the cell type I'm going to talk to you about is skeletal
muscle. No, this is not the [UNINTELLIGIBLE].
OK. So the point today is to look
at a particular cell type and how it forms. The type we've chosen is
skeletal muscle. Skeletal muscle is one of three
kinds of muscle in your body. The other two being cardiac in your
heart and smooth muscle around your internal organs.
Skeletal muscle acts in a voluntary fashion to allow movement.
It's an extremely complex structure. The final form of skeletal muscle
includes 200 proteins which have the extraordinary property of
contractility in response to nerve input.
I'm not going to talk about the contractile process,
although it's fascinating. And you're not going to be tested
on this for the physiology of contractility either.
But if you're interested in this, I would suggest you look at Chapter
47 in your book which talks about this quite nicely.
Skeletal muscles are arranged in large groups of fibers.
And each muscle fiber is a multinucleate cell,
is a giant cell that consists of many myofibrils or myofibrils that
are together in a sheath and are surrounded by many nuclei.
So skeletal muscle forms from the fusion of many mononucleate cells to
give a multinucleate syncytium. And during the process of skeletal
muscle formation there are a number of steps that one can delineate.
One can talk about a kind of cell called a myoblast which is a single
mononucleate cell --
-- that then fuses to form, through many steps, something called
a myotube which is multinucleate. And these various myotubes come
together to eventually form a muscle fiber.
Muscle is obviously an extremely
important cell type for movement. All of the meat that you eat, if
you're a meat eater, is muscle, essentially a skeletal
muscle. And there are many diseases that are associated with abnormal
skeletal muscle. Muscular dystrophy,
for example, is a deficit of one particular protein in the muscle,
affects one in about 3,000 boys. OK. So the myofibril is a very
beautiful construction of many proteins organized in a very ordered
structure. And the deal is that these proteins slide relative to one
another during contractility. And all of these bands of proteins
slide in an ordered fashion relative to one another as the muscle
contracts. It's an extraordinary story in physiology itself.
And I regret I don't have time to go through it with you.
But I want to use this rather as an example of a cell type and to
explore with you how the cell type forms during development.
So the story I'm going to tell you has to do with a particular
transcription factor called MyoD. MyoD, shown in green here, no, not
shown in green here. That's the DNA double helix.
Shown in red here binds to a particular sequence on
DNA, its target site. It binds as a dimer.
And it acts to activate the transcription of genes required for
muscle formation. OK. So MyoD is a transcription
factor. And, as I'll tell you a moment, it gives rise to the
determination of skeletal muscle. Now, I'm going to tell you a few
things about this that are general principles of how this transcription
factor works and then I'll go through some slides with you.
MyoD is both necessary, although I'm going to clarify that in a
moment, and sufficient for muscle determination.
This is a dyad of words that is very important, necessary: required for,
sufficient: enough to. And whenever you're thinking about gene function,
this is the dyad you want to think about. It may not be a gene,
and then I'll tell you in a moment. I'm going to put a caveat here with
respect to the necessary, OK? But necessary and sufficient is
one of these litanies that you want to ask yourself when you're thinking
about regulatory factors. The other thing that I want to tell
you is that MyoD is a member of a gene family. What's a gene family?
A gene family is a group of genes with similar structure and often
similar function. This gene family that MyoD belongs
to is called the MRF gene family, which stands for muscle regulatory
family. And there are four members.
And these members share some
function with one another. And that leads us to another term
which is the term redundant. MyoD is an extremely important gene.
And if you make knockouts in mice there is some phenotype,
but they have muscle. And it's not until you make a gene
mutation in another member of the MRF family that you see mice that
don't have any skeletal muscle. So redundant in this case refers to,
or in all cases refers to shared function. It can also refer to,
and does in this case, it can also refer to alternate pathways.
So the notion that we have is that we're starting here as an
uncommitted cell and we're going to end up over there as a
differentiated muscle cell. And we can get there by walking
straight this way, but we could also get there by
walking up and out the back and all the way around and to that same spot
in front. And both of those would be bona fide pathways that would get
you from point A to point B. So sometimes there can be alternate
pathways that will get you along the path of forming particular cell
types or even carrying out some kind of biochemical function.
OK? This is a general principle of biology. So let's look at this in a
bit more detail with some slides. The notion is that MyoD binds to the
promoters of many different genes expressed in skeletal muscle,
together with other transcription factors, some of which may be common
to all of these genes and some of which may be different.
And it activates their transcription.
And you can see I haven't drawn the genes in a really accurate way.
These are just representations. There's no double-stranded DNA
meant to be implied or not implied there.
MyoD is sufficient to activate the skeletal muscle program.
And this is a very exciting finding about 15 years ago when it was shown
that one could take the MyoD gene, and you actually put it in a virus,
and then you can infect a group of cells that normally wouldn't become
muscle with this virus. And lo and behold the virus that is
expressing the MyoD protein will turn these cells into
skeletal muscle. And this was the first example of a
regulatory protein that could take one cell type and turn it into
another cell type. And MyoD and the other MRFs are
very good at doing this. They can, for example, take brain
cells and turn those into muscle. They can really take most cell
types and turn them into muscle cells. So MyoD is sufficient to
convert non-muscle to muscle cells. And this is actually particularly
extraordinary because, as I showed you in a one line
schematic on this board, forming skeletal muscle is a
multi-step program. You start off with these cells
called, they call them myotome cells, and then you get these things called
myoblasts which are dividing. The myoblasts start to align in
arrays. And then the cells fuse with one another,
which is really unusual for cells. I mean it's a really kind of weird
cell type. And you get these long tubes that have got thousands of
nuclei in them. And then the tubes start to make
proteins that align themselves in these very ordered ways that allow
them to slide relative to one another, and you get this
multinucleate myotube that has contractile function.
And what's really cool about MyoD is that it can start this whole process
which then follows one step after another. So it's been termed a
master regulatory switch because it can activate a whole cell
type specific program.
Now, in contrast, and this is what I was alluding to
on the board, knockout or removal, a genetic mutation of MyoD does not
remove skeletal muscle from mice. So this is a micrograph of muscle.
You can see the ordered myotubes from a wild type mouse.
This is a MyoD null mouse. And there's perfectly fine skeletal
muscle there. It's a little, there's a little less of it, but
it's still there and the mouse is viable. However,
if you go in and you make a double mutation in the MyoD gene and
another member of the family called Mif5, there is no muscle at all in
any region, or no skeletal muscle at all in any region of the body.
The other muscle, the heart muscle and the muscle
around the intestine, the smooth muscle is fine,
but the skeletal muscle is completely absent.
So we can say that the MRFs are necessary for muscle formation but
that MyoD is a member of a redundant gene family. And that seems to be
the rule in biology, that genes come in families,
and very often one can take over the function of another when one of them
is mutated. And that serves as a kind of fail-safe for making sure
that development works properly.
OK. So here comes something to think about that I alluded to before
spring break. I remember this. Don't know if you do. MyoD is,
in the entire embryo the MyoD gene is only expressed in the future
skeletal muscle. This is a picture of a frog embryo.
And you can see these stripes along the back of the frog.
These are regions of the embryo called the myotones.
They're part of the somites that I'll talk about.
And this is what's going to become the future skeletal muscle.
And this is where MyoD is expressed. And, brilliant,
only there. And now this is a chicken embryo and you see the same
thing. MyoD is expressed in these stripes along the back in the future
myotones of the somites. It's also expressed in the future
limbs as the muscle of the limbs is starting to form.
And so you're going to ask me, or you should, how does MyoD get
activated just in the future skeletal muscle?
Because in a way this is a copout. I've told you MyoD activates the
skeletal muscle program, and it's only expressed in cells
that are future skeletal muscle. Well, how does it know to be
expressed just in this one region of the embryo?
And to answer that question we have to actually go back to the dawn of
time to fertilization. And I'm going to take you through
some of the steps that will get MyoD expression into this particular
pattern that will allow the skeletal muscle to grow out in just the right
places of the embryo to give just the right amount and the right
position of skeletal muscle. OK. So. And to do that we are
going to pose some questions. And I'm going to start by telling
you something and then pose a question. If you look at an embryo,
you could look back at that chick one if you wanted to do or you can
look at this fish. Here is your fish fillet,
your skeletal muscle, and it is on the so-called dorsal or backside
of the embryo. So last time we talked about dorsal
and ventral as two of the so-called axis or positional coordinates in
the embryo. And the muscle arises from a region that is termed dorsal
which is the back. OK? So you might ask me,
how do you know this? And I'll tell you how I know this.
You should ask me how do I know this. OK, so I'm going to.
Having put questions into your mouths, I'm going to tell you how
you know during the development of an organism where a particular cell
type is going to arise from. And the technique I'm going to tell
you about is something called fate mapping. So let's begin with the
sentence muscle, and I'm talking about skeletal
muscle when I write muscle, arises from the dorsal or the back
of the embryo. OK? And so how do you know this?
How is this known? And it's known through use of a technique called
fate mapping. What is fate mapping? So this is very interesting. The
idea is to take a very early embryo, I've shown you here a fish embryo,
and to inject one or a few of its cells that you can distinguish by
some kind of morphological, obvious indicator from the rest of
the embryo. And to inject those cells with a dye.
So here we've used a fluorescent dye. And we've put that dye near
the site of the embryo that's got this bump. OK?
And as the embryo develops the cells will inherit that dye because
it's a non-diffusible dye. And that dye will be inherited.
And in the later fish, we're looking down now onto its brain,
you can see that the whole front of the brain is outlined with these
green fluorescent cells. And what this tells you is that the
cell you injected initially has gone on to give rise to this whole front
region of the brain. OK? So fate mapping tells you what
cells will become.
All right. I know it's on the slide, but it's important that you
understand this because it is distinguished from something I'm
going to tell you later. So you can do this for skeletal
muscle. And I'm going to talk about frog development because so much is
known. So here is a frog at the 32 cell stage. And one can see,
because of the size of the cells and because of pigmentation differences
I'll show you in a moment, which side of the embryo is what.
And I've injected a cell here that's called the C3 cell,
all these cells have got different names, with dye.
And later on you can see, in this thought experiment,
that the somites are labeled with the blue dye. So the C3 cell,
and actually the one on the other side of embryo,
are going to give rise to skeletal muscle. OK.
So the reason that I wrote on the board what was on the slide already
is that it's really important to distinguish what cells are going to
become from when they've made the decision to become it.
So the next thing we want to know is when cells decide what they're
going to become. And I can rephrase that by saying
when is the fate decision made?
And fate mapping doesn't tell you that. All it tells you is what a
cell is going to become, not when the cell has decided to
become that thing. For this you have to do some other
assay, and you do assays that are generally called determination
assays. And I'll show you an example of one such assay.
So here's our 32 cell stage frog embryo again with the C3 cell
labeled. And one can go into the embryo and dissect out that cell.
Frog embryos are about a millimeter in diameter. And you can use very
fine glass needles to tease out that cell from the embryo.
And you can grow it in a very simple culture method with just some
saline solution and the cell will grow fine and divide.
And you can ask whether that cell goes on to make skeletal muscle.
OK? Does it know that it's going to be skeletal muscle?
And the answer at this stage of development is no,
it doesn't. So if you remove the cell, grow it in culture,
it goes on to become these things called fibroblasts which are cells
that spread out in the dish. They don't fuse. They don't make
all these muscle proteins. And so the cell, although it's
destined to become muscle, has not yet made the decision to
take that leap of fate. However, if you wait a few hours,
and we're actually on your handouts now. If you wait a few hours and
you go and you remove the cells that have arisen from C3,
which are divided now. They're still labeled and you can
distinguish them because it's a very powerful dye and doesn't diffuse.
So you can remove that same group of cells a bit later.
And you can then grow those cells in a culture, in a simple saline
solution. And lo and behold they go on, after some hours,
and form multinucleate myotubes. They go on to form muscle. So
somewhere between the 32 cell stage and the stage of a much older embryo
of many hundreds of cells, the cells have made the decision to
go onto their particular fate. So something has changed in terms of
the regulatory genes that they're expressing, presumably,
that allow them to go and become muscle. OK.
So let's break this
down a bit more. And let's ask the question,
as to what inputs are required to turning on MyoD activation in a more
defined sense? And the first thing I'm going to
talk about is how the embryo knows where dorsal is. OK? So
dorsal determination.
And what I'm going to tell you is a very interesting tale of
determinants, of cell autonomous regulatory factors that are
specifically required to tell the embryo where the future dorsal or
backside of the embryo is going to be.
And I'll tell you that these determinants act to stabilize a
particular protein that is a transcription factor,
and this protein is called beta-catenin.
And beta-catenin, once it's stabilized,
so it is a transcription factor, goes on to activate a set of genes
that are dorsal specific genes, but not MyoD. We're not there yet.
Gene. G. I cannot spell, can I?
OK. So let's discuss this using your handouts.
This is a movie that I was showing you at the beginning.
Woops. Let's show it to you again because I want to point
something out.
All right. This is a four cell embryo. Maybe it's going to be an
eight cell embryo. Do you see how these embryos have
got some, two cells that are kind of darkly pigmented and two cells that
are lightly pigmented? Yeah? The lightly pigmented cells
are the ones that are going to be the future dorsal site of the embryo.
OK? That's where the muscle is going to come from.
And these cells on the other side, on the ventral side of the embryo,
that's where the belly is going to come from.
Now, how does this happen? Well, it happens, and I've
augmented the diagram on one of your handouts a bit so you'll have to add
a circle. It happens because of movement of these purple dorsal
determinants. And these purple dorsal determinants,
as I'll show you, move within the newly fertilized embryo.
In fact, within about 16 minutes after fertilization these dorsal
determinants have moved in the embryo and have told the embryo
where the future dorsal side is going to be. And the way they move
is that, in fact, the early egg and the zygote consist
of two kinds of cytoplasm, an outer sphere of cytoplasm that's
kind of gelatinous and an inner sphere of cytoplasm that
is more liquid. And in this outer gelatinous
cytoplasm sit these purple determinants. And when
fertilization takes place these move by a good angle,
at least 30 degrees relative to where they were,
and relative to this inner liquid cytoplasm, which is why I've got
this doted equator there to indicate that there is a relative movement of
these determinants. OK? It's not the whole embryo
that's moving. It's just part of the embryo that's
moving relative to the other part. And this movement of determinants
defines the dorsal and the ventral side of the embryo.
OK. Here's a movie to show you that.
OK. So this is a movie that is
about the first 20 minutes of fertilization.
And you can see here pigment moving from one region to another region.
Now, the pigment is not the determinants. It just moves with
the determinants. OK? So this is an indication that
there is stuff moving, actually, from the vegetal pole
region up towards this so-called animal pole region.
So the terms animal and vegetal pole indicate two different sides of
the radially symmetric egg. The animal pole is pigmented.
The vegetal pole is not. And they're just useful landmarks.
And, again, this is a frog embryo. Things may be similar in humans,
but we understand much more about frogs. So that's why I'm going to
tell you how things work in frogs. OK. So there is a manifestation of
these dorsal determinants moving. These dorsal determinants move by a
really fantastic process. They move on microtubules.
Remember microtubules? What part of the embryo,
what part of the cell were microtubules part of?
Anyone remember? Dredge back in your memories.
I heard something. Yes? Thank you. Cytoskeleton.
Yes. See me for a frog afterward. So the microtubules are part of the
so-called cytoskeleton. They are large rods of proteins,
polymers of proteins. And when the sperm enters the egg it brings with
it a centriole that is a microtubular organization center.
And what it does, in this series of three pictures,
is to take this mass of red microtubules that are oriented in
every which way, and it organizes them so they form
these beautiful parallel tracks of microtubules in the outer cytoplasm
or between the outer and inner cytoplasm of the egg or of the
zygote, of the fertilized egg. So the sperm nucleus or the sperm,
excuse me, the sperm centriole is organizing this microtubular array.
And it's on these tracks of microtubules that these determinants
move, kind of like train tracks. And I'll tell you in a moment, it
really is that way. So, oh, it didn't quite work.
But OK. So here is a zygote and here is this protein I've told you
about, beta-catenin. Now, in the zygote beta-catenin is
phosphorylated. And that renders it unstable for
various reasons. And it's also cytoplasmic.
OK? With the action of the determinants I've been telling you
about, by about the two to four cell stage, so very soon after
fertilization the beta-catenin on one side of the embryo,
the side where these determinants are has been dephosphorylated.
So there is a post-translational modification. Dephosphorylated.
And that renders it stable for various reasons.
It's no longer subject to protein degradation. It also allows it to
enter the nucleus. It allows it to act as a
transcription factor. So these determinants are changing
the stability and the protein structure of this beta-catenin
transcription factor. Beta-catenin is really an important
protein. This is a wild type frog embryo. Two wild type frog embryos.
The head, tail, here's the eye forming. In embryos that have been
depleted of beta-catenin you get these kinds of blobs that have no
dorsal structures at all. They've got no muscle. They've got
no nervous system. Nothing that would normally come
from the dorsal side of the embryo. So what is the identity of these
dorsal determinants? And, again, this you have partly on
your handouts. And the identity of the dorsal
determinants ergo is something that stabilizes beta-catenin and
dephosphorylates it. And what these are believed to be
presently are two proteins called GBP and dsh. OK?
You don't need to know the names. It's the principle that's important
here. But what's very interesting is that GBP and dsh proteins bind to
another protein called kinesin, and kinesin attaches or is part of
the microtubule system. So you get these determinants
attaching to the microtubules, and as these microtubules polymerize
and have a rotation associated with them, it's not quite clear they
rotate at this point, this GBP and dsh are associated with
the microtubules. And then these two proteins,
GBP and dsh, also called disheveled, inhibit another protein called GSK3
which is a kinase that phosphorylates beta-catenin and
renders it unstable. So you're getting here dorsal
determination. You can go think about this more
clearly. Dorsal determination because you are inhibiting
an inhibitor. All right? Complicated?
Yes. Beautifully understood? More or less. This is really the
most beautiful example that we know of how you get determination of a
particular region of the embryo. OK. So one step. We probably have
about 20 steps to go. And clearly we're not going to
cover them all so I'm giving you a little meander through the number of
steps that are involved. So another step informing muscle,
that I want to tell you about, is forming a particular kind of cell
from which the muscle will arise. So not only does muscle arise from
cells that are dorsally located. Muscle also arises from a cell type
called the mesoderm.
The mesoderm is part of a system of cells that are the earliest known
cell types in the embryo. And these are the germ layers.
And the germ layers consist of mesoderm, and also of two other
cells types called ectoderm and endoderm. OK.
And these cell types were discovered a lot time ago.
They're not differentiated cell types but they do have different
properties. They are stepwise along the way to becoming different things.
The mesoderm, shown in red here,
gives rise to the muscle, blood, kidney, heart and various
other things. OK? The ectoderm, for example,
gives rise to all of the nervous system, and the endoderm to the gut
and the lung. And they get their names from their position
in the early embryo. The endoderm is on the inside,
the ectoderm on the outside, and the mesoderm between the two.
OK. How does the mesoderm form? The mesoderm forms through another
complicated system. It forms through the action of a
transcription factor called VegT. And this is a maternally expressed
transcription factor. So we can distinguish maternal and
zygotic effects, genetically and in development.
VegT is maternally expressed. That means it is present in the egg.
VegT in term activates in just one region of the embryo another gene
called nodal. It's actually a set of genes. Nodal is
a secreted factor. It is actually a ligand and,
therefore, an inducer. And it is zygotically expressed.
So another principle, "zygotically X" for expressed,
and "maternally X" for expressed. OK.
This is one your handouts. So we're talking now about the same
time of development that we've been talking about but a different system
that is working in parallel. Here is an embryo. And I've shown
you between the 200 and the 500 cell stage that has got this VegT
transcription factor present in the nucleus. It's a transcription
factor. And you can find a concentration
gradient of this thing. In one part of the embryo at this
equatorial region there are low amounts of it.
Towards the vegetal pole there are high amounts. And where you have
this low amount of VegT you get a band of cells that's going to become
mesoderm. This mesoderm then goes on to express this nodal gene which
is a secreted ligand. And, for those of you who are
familiar with this, it's a member of something called
the TGF-beta family. So this gives you another set of
cells to deal with. And what I'm going to tell you now
is that to think about where the skeletal muscle comes from we have
to superimpose the two things I've told you about becoming dorsal and
becoming mesodermal. So the next thing we need to do is
to talk about the dorsal mesoderm. And we can write an equation here
where beta-catenin plus nodal makes dorsal mesoderm.
And I'll tell you that this dorsal mesoderm has a very special property
and a special name. It's called the organizer.
Is the dorsal mesoderm the future skeletal muscle?
I'm sorry to tell you it's not really. There's another step
involved. And I will tell you in a moment that the organizer is going
to induce the precursors of the skeletal muscle.
So let me write this down just to give you a sense of where we are.
OK. So let's move on here. And let's define dorsal mesoderm by
an equation. And, in fact, you can define this whole
process by an equation. But, of course, the genes that have
to be expressed and so on have to be expressed in a specific temporal
order. So it's not a simple linear equation. It's got a time component,
too. OK. So here we have beta-catenin on the dorsal side.
And we have mesoderm defined by nodal signaling in a band across the
equator. And if we superimpose them we get a region where both of these
factors are in the same group of cells. And where both of these
factors are in the same group of cells we get a special type of
mesoderm formed called the dorsal mesoderm or the organizer.
The organizer is a very famous piece of mesoderm.
And it is famous for this reason. This is a very old experiment that
was done in the 1920s where one could take a piece of donor tissue
from a donor embryo, that is the future organizer,
and move it to a host embryo, and put it on the side of the embryo
where the organizer wasn't. OK? So to put it on the ventral
side of the host embryo. And when this was done,
to the surprise of the investigators, because they really didn't do the
experiment for this reason, they found that they got these
conjoined twins. Conjoined twin embryos.
Here's your host embryo. And this is a second embryo that's
formed. And you could look at see where that piece of transplanted
tissue went. And when you did you found it was in a strip along the
back of the embryo, but most of the second embryo,
the conjoined embryo came from tissue that was the host
embryo tissue. In other words,
this piece of transplanted tissue had organized or induced a second
embryo, including all the skeletal muscle. OK? And including a head
and a brain and so on. This is a very famous experiment,
very famous piece of tissue. And for this experiment the Nobel Prize
was awarded to Hans Spemann in 1935.
Here are conjoined frog embryos made by transplanting organizers.
You can see they have two heads and they're joined at their tail region.
What about humans? Well, the same thing is true in human embryos.
Usually identical twin embryos will split somewhere between the two cell
stage and a very early stage where there is something called the inner
cell mass. And you get two identical embryos made and you get
completely separate embryos made. Sometimes, very rarely,
you get incomplete splitting of the embryo. And the organizer is split
in two in a human embryo, and you land up with human conjoined
twins. This is very rare. The survival of conjoined twins is
very rare. There are some instances, and I've put on your handout a
diagram of, these are actual girls who had been diagramed that were
just like the frogs, with shared heads, with a shared
trunk and separate heads. So the processes in frogs,
as far as we know, are very similar to those in humans.
Now, what I'm going to do because I have very interesting stuff I'd like
to finish this off, finish off here, but I see time is
creeping on, is to end off with a teaser. And to tell you that the
final step in getting MyoD on is to activate these things
called somites. And I'm going to take five minutes
at the beginning of next lecture to complete this and then we will move
onto our next topic. So thank you.