The Science of Everything Podcast - Episode 155: Embryology and Development

Episode Date: October 24, 2025

An introduction to the process of development, beginning with fertilisation and covering the stages of blastocyst formation, implantation into the uterus, gastrulation and its constituent cell movements, neurulation and the role of the notochord, and the beginnings of organogenesis. We also discuss the differences in gastrulation between protostomes and deuterostomes, along with the many specialised structures found in amniotes to protect the growing embryo from drying out. We conclude with overview of some of the genetic mechanisms government the development process, including Hox genes and their role in governing genetic regulatory networks. Recommended prelistening is Episode 25: Tissues, Organs, and Systems. If you enjoyed the podcast please consider supporting the show by making a PayPal donation or becoming a Patreon supporter. https://www.patreon.com/jamesfodor https://www.paypal.me/ScienceofEverything

You're listening to The Science of Everything podcast, episode 155, Embryology and Development. I'm your host, James Fodor. Today we're going to be talking about the process of development from starting with fertilization right through to the later stages of the development of the fetus. The focus is going to be on mammalian and specifically human embryonic development, although I will mention a few differences between different types of animals as we go. recommended pre-listening is episode 25 tissues, organs and systems, just for a bit of general background. And one of the reasons I'm doing this episode is to provide some useful context for the next few episodes where we're going to be talking about the evolution of life and the development of different types of animals.

And comparative development is very important for that. So I thought this episode would be useful as well as a good standalone topic. One thing that I'll mention is that I'm not really going to focus so much on the reproductive organs and things like the role of different hormones and reproductive cycle and so forth. I'll do a separate episode on that. Here we're just going to be focusing on particularly the development of the embryo. Until relatively recently, maybe the late 18th century, it was thought that semen contained a premature miniature person, a miniature infant, that then just becomes. larger and larger during development. And that was known as pre-formation.

A competing theory is known as epigenesis, which is the idea that an animal gradually develops its characteristics from a formless fertilized egg. And this view is now known to be correct and gradually supplanted pre-formation views in the 18th and early 19th centuries. So that's a bit of historical context. Now let's begin talking about the process of development. beginning with fertilization. So we're going to begin by talking about fertilization,

and then we'll move through talking about the blastuses stage, gastrolation and embryology, and then later stages of development, including neurilation, and organogenesis, and the development of the fetus. And we'll conclude with a bit of discussion about some of the genetic mechanisms of development, which is actually quite an interesting area. So let's start with fertilization.

When semen is released into the vagina, the sperm travel through the cervix, up through the uterus, and then into one of the fallopian tubes, which is where fertilization typically takes place. As you may know, millions of sperm are released at once, and only one of them typically, in most cases, will be able to actually fertilize the egg, so resulting in a single pregnancy. Occasionally, you can have instances where two sperm will successfully fertilize different eggs, and that can give rise to twins. Sperm are attracted to the site of the egg by the hormone progesterone,

Progesterone is secreted from cells which surround the developing egg cell, and it actually binds to a receptor on the sperm membrane, which triggers a interstellular cascade, which results in an increased motility of the sperm phlegelum. The sperm essentially has a little like head and a tail, which is the phlegelum, which beats so that the sperm moves along and propel itself. So high progesterone levels lead to greater activity of the phlegelum, which leads to it sort of swimming faster. So that's how it's able to sort of follow the direction of the higher progesterone concentration and find where the egg is. Now the egg cell has an extracellular matrix, which is sort of a bunch of proteins and carbohydrates and other adhered compounds called the zona pellucida. And this surrounds the plasma membrane, the cell membrane of the egg and helps to protect it and is also critical in fertilization, the process of sperm fertilizing the egg. Now, another important ingredient here is the acrosome. So the acrosome is an organelle, so that's like a little compartment that's inside a cell,

and it's a special organelle contained in the sperm at the very tip of the sperm, and the acrosome contains enzymes that are needed for fertilization. So what happens is, as the sperm, you know, it's swimming along, it's guided by progesterone, which is helping it to sort of swim faster and direct itself towards the egg that's, been released in the philogian tubes. As the sperm approaches the zonopulucida of the egg, so this extracellular matrix, the membrane surrounding the acrosome, which is at the very tip of the sperm, remember, it fuses with the plasma membrane of the sperm's head. So the acrosome is surrounded by its own membrane. It's an organelle that's bound by membrane, and then there's

the cell membrane of the sperm. But these two membranes fuse together, triggered by the proximity of the zonopulucida, and basically that dumps out the contents of the acrosone outside of the sperm. The enzymes that were containing the acrozone then help break down the zonolucida and allow the DNA from the sperm then to be injected into the cytoplasm of the egg cell, because the zonopulucida protects the cell membrane of the egg so that other stuff can't get in, and the only way that it will break down, usually, is if the enzymes containing the acrozone are able to reach the zona pellucer to help break down the protective envelope and thereby allowing rest of the head of the sperm to come into contact with the cell membrane of the egg cell,

thereby leading to essentially the fusing of the membranes of the two cells and an injection of the genetic material that is inside the head of the sperm. Now, when this happens, as the sperm makes contact with the membrane and injects its DNA contents, this triggers a reaction. series of reactions from within the egg cell to prevent multiple sperm entry because there's no point in having multiple copies of the genetic material. Remember that each of the gametes, the sperm, and the egg has a full copy of the genetic material, one from the sperm from the father and then the egg from the mother. Each is a gamete, so it contains just one copy of the genetic material rather than two copies,

which is what are somatic cells. Most of the other cells in the body have two copies of the genetic material. So the idea of fertilization is you bring, one copy of the genetic material of the father and one copy from the mother, bring them together, and now you have two copies, and that forms a complete set of the chromosomes necessary for then the organism to develop. Now, you don't want a third copy because that will, well, it's not just useless, it's actually harmful, and it will disrupt development.

We talked about that in previous episode of polyploidy and so forth. If you're interested, you can have a look at the genetics episodes. But anyway, so you only want just the one additional copy of the genetic material, So once the first sperm is entered, there's a need to prevent further sperm entries. And so the egg has a mechanism for that. Specifically, we have, again, calcium serving as a secondary messenger. That's also used release of the enzymes and the acrosome in the sperm. We've talked about it in previous episodes as well as the important secondary messenger molecule.

So calcium release in the cytosol of the egg cell triggers granules, which are basically a little storage. sites in the in the cytoplasm of the egg to release enzymes which then digest the receptor proteins that are found on the surface of the of the egg cell which the sperm latch onto so basically the sperm can't find it anymore or are not able to latch onto the surface of the egg cell and and release their genetic material so those are digested after the first the first sperm has made contact there by preventing what's called polyspermy or multiple sperms from releasing genetic material. There are additional mechanisms as well, so these granules also fuse with the plasma membrane and modified the zonopulucida so as to prevent further sperm entry.

So remember, the first sperm that contacts and successfully releases its aqua zone contents will digest the zonopulucida locally, at least, to allow it to gain access to the cell membrane. But then once it releases its genetic material, then that triggers another reaction which helps to alter the zonopulucida to prevent any additional sperm entry. So again, so the process can only happen once. So once the DNA has been essentially injected from the head of the sperm into the cytoplasm of the egg cell, paternal chromosomes then are released into the sinusole, and they migrate to, I'm not entirely sure what the mechanism is, but they migrate to the nucleus

and are essentially paired with the maternal chromosomes that are already there. That sort of completes the process of fertilization, and then we begin subsequent stages of development. Obviously, the genetic material will need to then be duplicated, and then the chromosomes pair up, and they're pulled apart, process of mitosis. Again, we've discussed this in previous episodes, so I won't go through that here. Just sort of understand the point that before that process can be triggered,

there needs to be the introduction of the extra genetic material necessary to form the full complement of genetic material. And then once that's happened, the chromosomes sort of line up with it. The chromosomes from the mother and the father are combined with each other. So now there's a full set in the nucleus, and then they serve as the basis for subsequent mitosis, the duplication of all of the genetic material in the synthesis phase, and then they line up and they're pulled apart by the mitotic spindle

and all that stuff that happens. Okay, so that's fertilization. Now we're moving on to the next stage, which is the formation of the blastocyst. So once the egg has been fertilized, it's now referred to as a zygote. So it's essentially, it's a single cell. Basically, it's the egg cell, but now it has the full complement of genetic material. And now it begins a process of cell division.

This process of early cell division is called cleavage, and it results in the formation of multiple cells. So, you know, it goes from one to two to four as cells divide. Each cell splits into two. And after a few days, this results in a hollow ball with a sort of a cavity, the middle and then it's surrounded by a thin layer of cells. And this hollow ball is called a blastocyst. Now initially, there is not much increase in the size of the cells. This happens later. Initially, what happens is that the cells just divide with the genetic material needs to be duplicated,

obviously, but the size of like the cytoplasm and things like that doesn't change very much. So you basically get a process of the, I mean, there's some growth, but it's mostly just the cell dividing, the initial cell dividing into smaller and smaller cells to form the blastocyst, the growth of the cells will happen later. In humans, the blastocyst then differentiates into an outer layer of cells, which is called troper blast cells. Then there's a cavity in the middle, which I mentioned. That's a ball and a ball of cells surrounding a central cavity. So that central cavity is called the blastocysts cavity. And then there's sort of a bump. So it's like a hollow ball, but it's not entirely

symmetric. There's sort of like a bump. And often in diagrams, this is shown at the top, the top of the hollow ball. So I'm going to ask you to imagine it there. And this is called the inner cell mass. So basically we have a hollow ball of cells, but with a sort of like a growth or an indentation, with a lump of cells at the top of the sphere, a lump going inwards. So it's a sphere from the outside, but on the inside there's like a bump that protrudes inward. And that's a bit of a larger mass of cells, includes into the blastocyst cavity. And this is called the inner cell mass. This will become very important because it's the inner cell mass where the eventually the embryo will form, but we'll get to that. So meanwhile, as the blastocysts

is forming and as cleavage is occurring, it's moving along the fallopian tube and eventually reaching the uterus. This occurs roughly at the fifth day after fertilization, again, in humans. Once the blastocysts has reached the uterus, or specifically it comes into contact with one of the walls of the side of the uterus, the blastocysts then sort of hatches out of the zone Pallucidus. So remember, that's the protective extracellular matrix that initially surrounded the zygote and now surrounds the Blastocyst. So the zone of Pallucida is actually what initially comes into contact with the wall of the uterus, because it's external to the rest of the blastocysts. So it makes contact with the uterus, allowing the blastocysts to sort of hatch out of that.

And then the outer layer of the blasts, the tropoblasts, remember, that's the outer ball of cells surrounding the hollow space within. tropoblast then come into contact and adhere to the endometrial cells of the uterus, so the cells on the wall of the uterus. And then in a couple of days after that, the zonopulucida disappears, which exposes the tropoblast, which attaches to the endometrium and it implants there. So at this point, by about a week after fertilization, the zonopulucida, the extracellular matrix has served its purpose. And we now have the troperblast making direct contact with the endometrium cells in the uterus. and it implants there, and so it's sort of stuck on the side of the uterus and progressively grows out from there. Obviously, that's necessary because you need to have blood supplying nutrients and things being exchanged with the mother.

I will talk more about the uterus and, you know, thalopian tubes and the hormones involved in that. In a subsequent episode here, I'm really just interested in the embryo itself. So to try to keep the episode a reasonable length, we're going to focus really on what happens in the embryo, I'm not going to talk so much about the uterus. Obviously, though that is very important. So the other thing that I should mention is it's going to get a little bit complicated from now on as to exactly what's happening with the embryo and the different stages. I'm going to do my best to explain it without diagrams.

That's what we do here. In doing so, I'm going to describe different shapes that things form as a way to just help visualize different stages and different processes. But you should bear in mind that these are highly idealized shapes. And in general, the way that they're depicted in diagrams is that you describe the shape of the embryo in its surrounding membranes without reference to the uterus. So you just pretend it's sort of like by itself. And so, for example, when we talk about something being a sphere, in practice it's unlikely to be a sphere because it's connected to the uterus. It's implanted into the endometrial cells of the uterus.

And so that kind of, it means a sort of squashed or it's not a full sphere, right? And in fact, a real shape is quite complicated. So don't take the shapes that I'm going to explain too literally. It's more about the relative positioning of different things and what's inside something else. You'll see what I mean in a moment, but just bear that in mind when I'm going to be describing some of these processes. One other thing I should mention is that different diagrams often show things differently when it comes to embryonic development. And this can be very confusing if you're trying to compare different sources, as I found out preparing for this episode. There's a few things to bear in mind.

One is that there are certain organisms that have been studied for the purpose of understanding embryology. So people have studied humans, but there's ethical guidelines about how long you can develop human embryos, something called the 14-day rules. You're not allowed to go beyond 14 days developing an embryo in vitro to study it. So a lot of studies have been done obviously in mice as an analog in mammals, but also in sea urchins is a common organism that's been studied, as well as in frogs. So a lot of diagrams that you'll see actually show, especially in the earlier stages, will show what the process looks like in sea urchins or in frogs. So just be aware of which species you're looking at when you're looking at the stages because the diagrams can look different. Also be aware of what perspective is being drawn, whether it's sort of like a side view or a top-down view, especially later on as the embryo becomes less symmetric, that becomes important. And what it's including, what it's not including, particularly which membranes are included or not included, because again, this can give rise to sort of confusions about exactly which things are being included.

shown. So anyway, let's keep going and focusing on human development. Many of the same phases occur in other animals, but the details do differ. And this is something we'll talk about in future episodes when we talk about more comparative development. So at this stage, we have the blastocysts that's formed and it's implanted in the wall of the uterus. I should mention that sometimes the blastocysts implants in the wall of the fallopian tube, and this is called an ectopic pregnancy. And these, as far as I know, never result in a viable offspring and will always either abort spontaneously or result in a miscarriage or sometimes we'll need to have intervention to resolve that. So these are very dangerous. There's quite a lot of different things that need to

happen for a pregnancy to go correctly, and there are actually a lot of points of failure that can result in spontaneous termination of the fetus or miscarriage. We'll cover those in a future episode, I'm not going to focus too much on those. But just be in mind that when I say that when I talk about the things that happen next, I'm talking about when things go typically and when there's no pathology or unusual disruptions in the process. Okay, so now I'm going to move on from talking about the Blaster System. We're going to move towards the next phase of embryonic development, which is called gastrolation. This is a very complex phase, and in some ways the most important phase of the development of the embryo. It's also very important

for understanding comparative development across different types of organisms, and I'll comment on that briefly. So what is gastrolation? Gastrolation involves the development of multiple layers of cells in the developing embryo, so these are called germ layers or germinal layers. All of the tissues and organs and other cells of a mature animal can trace their origin back to one of these germinal layers. There are two main types of animals, well, actually sort of three. So there's the sponges, they don't have differentiated tissues at all. But of the other two that do have differentiated tissues, there are essentially animals that have two germinal layers and those that have three.

So these are called diploblastic and triploblastic organisms, or animals specifically. Now, most animals that you would likely be familiar with are triploblastic. That means they have three germinal layers, the ectoderm, the mesoderm, and the endoderm. And that's an instance where we have sort of nice intuitive names. So ecto effectively meaning like external, meso in between, and then endo in the interior. And that describes where they at least initially form in relation to the emberra. They move around a lot later. So the diploblastic animals are mostly the niderians.

So these are organisms like jellyfish or jellies, as they should be called, because they're not fish. So they do have differentiated tissues, but only have two layers. They don't really have like an internal gut, like most other animals. do. So most animals are triploblastic. They have these three germinal layers, and these three germinal layers originated a very long time ago early in evolution, and that's why they're shared by these different organisms. So gastrolation, as I said, is the process by which these different germ layers develop and differentiate from each other. During the process of gastrolation, the cells involved in these different layers, in these different germ layers, need to differentiate

from each other, move in relation to each other, and fold, extend, flatten, and sometimes even literally, like, migrate, like, not just move relative to another cell, but actually leave a sheet of cells and migrate in the interior of the embryo, like moving through a fluid-filled matrix. So there's a lot of complex things that are happening here. We can summarize some of these processes in five different types or categories of cell movements or relative changes. Just to understand some of the complexity that's happening here. So these are epiboli, convergent extension, invagination, ingression, and involution. So most of them start with in, right?

So don't worry too much about the names. Just trying to get a flavor of what types of processes are happening in gastrolation. So let's start with epiboli. So this is the expansion and finning of one sheet cell to, to spread over and enclose other cells. It's, by the way, helpful to think about these different types of movements as initiating from a sheet of cells. This is because at the start of gastrolation, what we have is, remember, a hollow ball, when I say hollow, it's filled with fluid, but like there's no cells in there. A hollow ball with the inner cell mass at the top.

So the hollow ball is just the sheet of cells. That's the trooper blast cells that are surrounding it. And then the inner cell mass is a fairly thin conglomeration of cells. So a couple of sheets of cells that are stacked on top of each other or sort of intermingling a bit with each other. And often when tissue develops, it comes in the form of sheets of cells, either a single sheet or maybe a few stacked on top of each other. So there's a sort of a linear arrangement of the cells. So often what happens in gastrolation is we start with a sheet of cells,

one or more cells stacked on top of each other in a sort of orderly, relatively orderly fashion. And then something will happen to modify the. arrangement of the cells in that sheet or even disrupt the sheet structure. So epiboli refers to the expansion and thinning of one cell sheet to spread over or enclose another. So you can see where this is important because if we have two layers of cells and then there's a need for one to wrap around another, then the one that does the wrapping would need to sort of stretch and enclose the other one. So epiboli refers to that process. Then there's convergent extension. So this is where cells intercalculate, which means move between and interspersed one with another. So this can

occur when you have, say, one layer of cells on top of another, and then you want to interspers those layers together, so mix them up. So then instead of having layer one of cells on top of layer two cells, you have a single layer of cell one and then cell one and then cell two, right? So that's intercalculation. So this results in a tissue becoming longer and narrower. And you can see how that would be important during development, right, because you want some tissues to change shape. Invanation involves the infolding of a sheet of cells into the embryo, so that's sort of more intuitive, right. Invanation forming an in-pocketing or an infolding, and that's important for changing of shape and movement of cells. So now it goes from being linear to being pocketed inwards. There's

involution, which is sort of like in vagination, except instead of just sort of resulting in in a bending or an infolding. It's an infolding and then a twisting or like a rolling underneath. If you imagine having like a piece of paper, you push it inward so that it like bows inwards a bit, that's invagination. But then if you imagine pushing it inwards and then sort of pushing that in a bit to one side so that it rolls up underneath where the initial sheet is. So you roll up a little bit underneath the other one if you sort of see what I mean. That's involution. This is very important for forming in-pocketings that then go underneath the surface of another one, of the other layer, which can be used for stacking sheets on top of

each other or forming pocketings that can then, you could then imagine pinching off that pocket and then forming a, essentially a new hollow ball of cells underneath the initial membrane. If you invaginate, roll, and then pinch it off, then you've got a hollow ball that was underneath the initial layer of cells. And then the final type of movement's ingression. So this is sort of the most radical in some way. So here you have an initial sheet of cells. And then some of the individual cells, not the whole sheet, just individual cells from within the sheet, leave the sheet, and they go inside towards the interior of the embryo, like inside moving out of the sheet into the extracellular matrix, and they're moving around so that they become physically detached from other cells.

Cells usually exist next to an indirect physical contact with other cells. In fact, this is one important mechanism keeping cells where they're supposed to be and preventing them from interfering with other cells. One of the mechanisms of cancer is important processes that leads to development of cancer, especially metastasis, is when cells become detached from the sheets or matrices that they're supposed to be embedded in and then can move around. And that's usually quite dangerous. There are obviously certain types of cells that are supposed to do that, such as white blood cells, which are part of the immune system and they move around the bloodstream. But in general, most cells should stay kind of anchored where they are. But in this phase of development, the ingression of cells, and movement of the cells through an extracellular matrix is important to be able to physically distinguish two populations of cells. So it's almost like the cells are literally like picking up shop and migrating over to somewhere else. And when their cells do this, when they become sort of itinerants and loose, they're called mesenchymal cells. So they're sort of loosely clustered, maybe, but they're not tightly adhered and connected to something else. So these mesenchymal cells

will come up later. So through these processes of epiboli, conversion extension, invagination, involution and ingression, we have different ways in which cells can move in relation to each other. Sheets of cells can become extended or pushed inwards or twisted, rotated with respect to each other. These sorts of motions are critical for gastrorelation to occur because what we have to happen is not just that the different types of cells differentiate and then become different, but they also have to move into the right places and form the right shapes. So let's talk a bit more about how that works at a larger scale. We've talked about some of the mechanisms at the cellular level,

but what's sort of happening at the level of the whole embryo. So here I'll make a distinction between what happens in amniotic organisms and what happens in non-amniotic organisms. Amniotes are more recently evolved organisms that are specifically adapted for life on land out of the water. And so amniotes form a clade, which means that they all descend from a common ancestor, and it's all of the organisms that descend from that common ancestor. And specifically, amniotes are mammals, reptiles, and birds. And so they differ from, say, amphibians and fishes, as well as all the invertebrates, in many important ways. We'll discuss this in more detail when we get

to the episodes on the development of life. From our purposes here, what I'm emphasizing is that There are important differences in embryology between amniotes and non-amniotes. In non-amniotes, gastrolation, the process of differentiating of the different germ layers, gastrolation is relatively simple. I mean, look, it's still kind of complicated, but it's a bit simpler than in amniotes. And the reason is because amniotes have a whole bunch of extra structures that they need to form in order to prevent the embryo from drying out, because the embryo needs to be able to exist on dry land. particularly think about laying an egg versus laying an egg on land versus laying an egg in water, right?

Or in mammals, they actually, the live, young gestates within the mother, so there's additional processes that need to happen there. But the point is that there's a whole lot of extra processes that are needed to make that possible. In non-namniotes, those aren't needed, and so gastrolation can be a bit simpler. Basically, what happens is you have your blastocyst, right? So this is your hollow ball with an inner cell mass. Not all organisms actually have the inner cell mass at this point, but let's not over-complicate things. you basically have a hollow ball of cells and one side of which then begins to invaginate. So bends inwards and pushes up towards the other side so that instead of having a hollow ball,

you now have kind of what looks like a bit of a horseshoe, except the horseshoe consists of two layers. You've got the outer layer and the inner layer, the one that's invaginated and pushed up into the other one. Now this initial entrance, or effectively a hole that's formed when this invagination occurs during gastrolation, this is called the Blasterpour. So this is the hole, basically a gap between the two layers of cells, inside of which is still contains a pocket of fluid. So remember, there's initially, with the blastocysts, we had a ball with fluid in the middle. The fluid is still there.

It's not like it all leaks out. It's still retained. but now there's been an invagination so that it's not a hollow sphere consisting of a single layer of cells, it's a hollow sphere consisting of two layers of cells, but with one opening where the, you know, one side invaginated and pushed inwards. And so this hole, this sort of entrance into the interior of the ball, is called the Blasterpore. And there's a very important developmental distinction between two large groupings of animals called protostomes and deuterostomes.

Protostomes consist of many types of invertebrates, including arthropods, like so all insects and spiders and scorpions and things like that, as well as mollusks, so snails and squids and so forth. So those are all protostomes, as well as a bunch of other types of worms and things. Duterostomes are mostly chordates, like that's your vertebrates, essentially, and echiniderms, so starfish. and one or two other types of worms. So there's sort of this big divide, tripler blasts, into your protostomes and judoen. Again, we'll talk more about this later, but the basis of

this distinction, like the developmental basis of the distinction, is in, relates to this blasterpore, this opening that develops in the blastocysts. The difference is that in protostomes, the blastapore becomes the mouth. So protostom means first mouth, whereas in judoostomes, the Blasterpore becomes the anus, so Jeterosome means second, so Jeteros don't mean second mouth. So the mouth forms later. It might seem sort of trivial, like, well, what does it really matter? But this difference represents a fundamental sort of divergence in evolutionary development, because this occurs very early and is very sort of consistently different in these two branches of life. So it's one of the reasons I wanted to emphasize the embryological development before we get to the,

before we cover the history of life, because we need to be able to understand why these distinctions are made, and a lot of that relates to early embryological processes. So in protostomes, the blastopole becomes the animal's mouth, and that in-pocketing eventually becomes the digestive tract, well, other organs as well. But to simplify things, you can imagine that that blastopole hole becomes the mouth, and then the space within it becomes the digestive tract and you have the other organs,

and then eventually there will be another hole at the other end of the organism, which is the anus. Whereas in judoerostomes, it's the other way around. That initial hole becomes the anus, and then later on the mouth will be formed at the other end. There are other differences between protostomes and judoostomes as well, so it's not just about the blastopore being the mouth or the anus. There are other differences, such as the way that cleavage occurs. So remember, cleavage is the process of differentiation just after fertilization,

where the zygote, the fertilized egg, differentiates into two, and then four, eight, 16, 32 cells. And for the most part, these cells don't increase in size. So the overall size is fairly consistent, but they just split up so that each cell becomes smaller and smaller, again, at least initially, before the blastocysts forms. So cleavage occurs in both protostomes and deuterostomes, but it occurs in slightly different ways. So in protostomes, they have something called spiral cleavage, where effectively there is the easy, where to describe it is that there's a sort of a spiral relationship between the different cells, the sort of spiral around each other. Whereas judaous terms have something called radial cleavage,

where they don't spiral around each other, they sort of are evenly distanced from a central point. It's hard to explain this without being able to visualize it, and it doesn't matter too much for our purposes. I'm just emphasizing that there are other differences in development as well. Now, as I've mentioned, development is different in different organisms, and particularly when we're talking about gastrolation, it's quite significantly different, even if there are underlying commonalities. The gastrolation is much simpler, relatively speaking, in non-amniotes. So particularly common organisms that have been studied are frogs, so frog embryos, and the sea urchin. So in those cases, you have the impocketing of one side, which then forms the blasterpour.

Eventually, that impocketing then sort of opens up another hole on the other side. So you've got essentially an interior tube that goes from one side of the animal to another. This becomes the digestive tract. Then what happens is that alongside this is a differentiation of, remember, the three different germ lines. So the outer cells become the future ectoderm. The cells that inpocketed, that invaginated inwards and formed the size of the digestive tract, those become the endoderm. And then there are other cells which ingress from the endoderm.

So remember, that means that they basically, you know, pack up and move out from the sheet of cells and they move into the hollow space and differentiate and become, they become mesenchymal cells, so they become detached from the sheet, and then they differentiate and become mesoderm. So the mesoderm is in between the endoderm and the ectoderm. This is particularly what we're looking at here is the sea urchin, so it's sort of a very simple case where you can sort of easily distinguish the three different layers. So just to recap, initially, we basically have a hollow ball of cells

with a single sheet of cells around the outside and then a fluid-filled space in the middle. We then have one side of that hollow ball, one part of the sheet of cells, begins to invanionate inwards. This is actually called the vegetal pole, if you're interested, begins to invanionate inwards. As that's happening, the cells that are part of this infagination

that begin to poke inwards, begin to differentiate, and they begin to form a mesoderm, whereas the other cells left over that are still around the outside, those become ectoderm cells. Eventually, the endoderm continues to invaninate and then reaches the other side, where it forms the mouth. So now we have basically a tunnel that goes through the center of the organism, which will form the digestive tube, that that is lined by endoderm cells.

Meanwhile, we've had these mesenchymal cells, or these cells leaving the digestive tube, or what will become the digestive tube, they're leaving, they're becoming mesenchymol, They're entering the fluid space that surrounds the digestive tube, and they differentiate in form mesoderm. So this is an illustration, again, particularly talking about in sea urchins, though it's similar in other organisms, but a bit different. This is the process by which we have the formation of the mouth, the formation of the anus, the formation of what will become the digestive tube, linking sort of the two sides of the organism with a tube that goes through the middle, as well as the origins of the three germinal layers. so extoderm, mesoderm, and endoderm. And those are the major components that happen in gastrolation.

These are all critical because then these different germ layers will then go on to form different types of tissues and organs in the organism. Now, in all organisms, the different germinal layers form similar types of tissues. Obviously, not every organism has exactly the same organs, and there's differences of structure and function. but in all cases the germ layers give rise to pretty similar subsets of tissues across all types of organisms. So the ectoderm, that's the outermost layer, that always gives rise to the skin and the nervous system. Then endoderm, so remember that's the cells that invaninated and eventually formed the wall of the gut, these give rise to the digestive tract, well that makes sense, and we just talked about that, as well as the lungs, which also kind of makes sense. because these are also, the lungs are also an organ which interfaces with the outside.

You know, the air goes in and fills the lungs, kind of like the digestive system also interfaces with the outside. So that kind of makes sense as well. Endocrine glands, as well as the liver, which obviously has a close connection to the digestive tract, so maybe that kind of makes sense. So then the mesoderm gives rise to pretty much everything else. So this includes the muscle, muscles and the skeleton. So these give support and structure to the body, as well as the kidneys and a reproductive system. But you can kind of see that there's some logic to it, particularly with endoderm leading to the digestive tract, ectoderm being the skin, and then mesoderm being the kind of support muscles and skeleton that exist kind of in between those. This pattern

of diversification has remained consistent from a very early stage in the development of animals, and that's one way we can tell that it's sort of very fundamental and important to shaping the how it is that an embryo becomes differentiated and formed and all of the different parts are doing the right things, that this very early process of differentiation that occurs, that begins in gastrolation. Now, so far I've been talking about gastrolation in a fairly general context, as well as talking about gastrolation in invertebrates, like the sea urchin, and I mentioned a bit about the difference in protostomes and deuterostomes. Now I'm going to tell you about more of the details of what happens in mammals specifically. A lot of what I'm going to be talking about

applies generally to amniotes. So remember, that's also birds and reptiles, but there are some differences there, obviously, because they lay eggs, whereas mammals give birth, most mammals are alive young. So I'm going to be talking about mammals, and obviously in the particulars, in humans. Basically, the more different the animal is, the more differences they'll be, but there's commonalities across all amniotes. Anyway, so gastrolation always involves a differentiation into these three tissues, ectoderm, mesoderm, and endoderm, and it always involves this sort of of in-vagination or in-pocketing of one of what will become the endoderm layers into what will become the ectoderm layers, which then forms the gut. So those things always happen. It's just in mammals,

it's much more complicated, and there's a bunch of other things that happen as well, in amniotes generally. And a lot of that relates to the needs to provide extra protection for the growing embryo, because unlike other organisms, amniotes can't rely on laying eggs in water. Life originated in the oceans, as did animal life, and so most early forms of life, and so to this day, most, or at least most types of animals, lay eggs in water. So that's initially what was developed for. But amniotes evolve specializations, especially when we're talking about larger animals, specializations to prevent the drying out of eggs. So as I mentioned before, a lot of the extra structure and components of gastrolation in mammals and amniote, more gentlemen,

generally relates to the need to provide extra protection for the embryos due to the need to lay eggs on dry land or to support life young growing in the mother directly. So let's talk about how this works. So we begin around day nine, as before, with our hollow ball, remember the outer layer of cells are called the tropoblast cells. We've got the blasted pore cavity, which is an inner fluid space, and then we've got the inner cell mass at the top, a fairly small mass of cells sort of at the top of the sphere. Now, the first thing that happens is that the inner cell mass differentiates into two different layers, epiblast and hyperblast. These layers then form separate stacked disks of cells, which are now called the bilamina disk. Okay, so this is where it can

get a bit confusing, especially if you're looking at different diagrams. So let me try to explain what what's happening here. We've got the outermost layer, which is basically a sphere. That's the trophoblast. I'll explain what happens to that in a minute, but that doesn't actually give rise to any of the embryo. That's a protective membrane. Within that we had the inner cell mass. The inner cell mass is now just differentiated into two layers, epiblast and hyperblast. Each of those layers in turn then goes on to form essentially its own like mini pocket, so mini encapsulated envelope of cells with a fluid-filled cavity in the middle, within the tropoblast. So the topmost layer, again this is just the way it's often shown,

The topmost layer, the layer that's closest to the outside of the trophoblast, is the epiblast, and that gives rise to what's called the amniotic cavity filled with amniotic fluid. I'll discuss that a bit more in a moment. The other side, closer to the middle of the hollow ball, the hyperblast, that gives rise to the yolk sack. So we've got these two different envelopes, which are like hollow sacks, one on top of another, all surrounded by the big hollow ball with the trophoblast cells forming the outer layer. Now, in between the developing amniotic cavity and its amniotic membrane, and the yolk sac below it, is a flat disc of tissue, which is called a bilamina embryonic disc.

This, at the moment, is just a flat disk of cells, is what will actually give rise to most of the tissues in the embryo. Some of the tissues do also come from the yolk, but mostly it comes from this bilamina disk. So it consists of a layer of hyperblast cells on the top and a layer of epitoblast cells below. And it's mostly this bilaminar disc, which will actually give rise to the embryo itself. So these structures all form by about day 14. So starting from day 8 or 9 and up to day 14, the inner cell mass differentiates into epiblast and hyperblast, and then these two layers in turn further differentiate to form, that the epiblast forms a membrane called the amniotic membrane, which surrounds the amniotic cavity, so that's nearer to the outside of the ball.

Nearer to the inside, the hyperblast differentiates to form the yolk sac. So again, that's just a layer of cells with a fluid in the center. And then in between the amniotic cavity and the yolk sac, there is this thin layer of cells, a flat disk of cells called the embryonic disc, which mostly will give rise to the future embryo. So what we have is an outer layer of cell, a spherical layer of cells, trooper blast, containing a mostly empty internal cavity, blastocyst cavity, we've mentioned that before, except part of the blastocyst cavity has now been displaced by an additional two extra, essentially membrane-bound sacks, one the amniotic cavity, the other the yolk sac,

in between those two membranes-bound sacks is the embryonic disc. So just to count, we have currently three membranes enclosing three different internal fluid-filled regions. So the blast-sill or the blastocyst cavity, the yolk sac, cavity inside the yoke-zac, and the amniotic cavity, surrounding by the amniotic membrane. and each of them has a slightly different composition of the fluids, and we'll talk about what those do later. Each does a different thing. But at the moment, I'm just describing the structure. Okay, so hopefully this is slightly clear as to what's happening, because diagrams don't always emphasize exactly how these membranes relate to each other. In humans, gastrolation begins around day 14.

So that's when we have this triple membrane, triple-hawlossack structure forming, as I just described it. So once that's formed, day 14, gastrolation begins. begins. And it begins, its commencement is marked by a very specific event, and that is the formation of a structure called the primitive streak. The primitive streak is visible. You can see it. It's a morphological marker of the beginning of gastrolation, and it looks like a linear band of cells on the embryonic disc. Remember, I described the embryonic disc as a kind of a flat, oblong disc of cells, just sort of sandwiched between the amniotic cavity and the yolk sac. Well, now, instead of imagining that flat disk from the side, so it looks flat, imagine we

rotate of you, so we're looking on the top of it. So now it looks like an oval. If you look on the side, it's flat, but now we're looking down from the top, and it's an oval, right? So this embryonic disc, this flat disk, actually forms essentially a line. So you can imagine imagine a little dot appearing around the middle of the disk. It's not exactly the middle, but whatever. And that dot then kind of extends out to the side as a line, like a visible line of cells or cells that are differentiating. They're changing, which is why you can see them. This is the primitive streak. So it's a line of cells that extend linearly from sort of the center of the embryonic disc to the edge of it. And these cells are differentiating in a particular way.

Something's happening to them which makes them look physically different, but it's not the fact that they look different, which is important. That's just like the morphological sign of it. It's what's happening that's important. And I'll explain in a second what's happening when the primitive streak occurs or develops. But the formation of the primitive streak marks the beginning of gastrolation in humans and in all amniotes. Now, what is happening when the primitive streak occurs? Again, it's not like it's appearing there just so that we can tell that gastrolation happens, right? Why does a primitive streak occur? What makes it do that? Well, what's happening is that epibblast cells

around the center of the bilamina disk begin to differentiate and move inwards, inwards meaning towards the interior of the embryonic disc. And we mentioned that process before. That's called ingression. So the cells are differentiating and they're packing up shop, they're leaving, they're going inwards. So they're forming mesenchymal cells. Remember, that's when they sort of detach from their sheet and then they move. So these mesonchymal cells, will eventually form the mesoderm. So we talked about this before. In non-amniotes, they don't have a primitive streak, right? These mesenchymal cells that eventually form the mesoderm just come from cells that form the side of the digestive tube after the invagination, right, that happens with

gastrolation. It doesn't quite work that way in amniotes because things are more complicated. Instead, we have this bilaminar disc which forms, and then the primitive streak forms along like one linear stretch of cells, which then begin to differentiate, begin to ingress, and become mesenchymal cells. Again, in both cases, we have a process that gives rise to the mesoderm, but we get there in a different way. As I said, it's more complex in the amniotes. So these mesencomal cells form the mesoderm. The epiblast cells that were left behind, where the mesencom cells came from, these go on to form the ectoderm, and then the hyperblast cells, form the endoderm. So just to remind you, remember that initially we had the inner cell mass,

that sort of blob at the top of the hollow ball, and that differentiated into epiblast on the top and then hyperblast below that. So the epiblast cells eventually become the ectoderm, except for the ones that form the primitive streak and then become miscarmosals, those become the mesoderm, and then the bottom layer of cells, the hyperblast, those become the endoderm. So that's why this inner cell mass and the subsequent differentiation is important, because those two layers will eventually form ecto and endoderm genital layers, and then some of the epibblast cells that differentiate and become mesenchymal in the primordial, beginning with the primordial streak, those become the mesoderm.

So that's where we get those three layers from in amniotes. And those three distinct layers all formed by about daph 19 or so, so about five days after the beginning of gastrolation. So it happens relatively quickly. So let me now explain what happens at a larger level. So this bilamina disk, which then forms the primitive streak, and we have the mesonymocels forming and the cells moving in relation to each other, continues to differentiate so it gets thicker, it gets longer. And also these two cavities, remember the bilaminaridisc is sandwiched between the amniotic cavity above it and the yolk sac below it. These cavities are also expanding, so they're growing.

but they grow in a certain way. So what happens is that the amniotic cavity kind of grows sideways and surrounds, begins to surround the bilamina disc, which eventually becomes the embryo. So as I said before, the biolamina disc mostly becomes the embryo. It's a little bit more complicated, but you can think of that as the embryo itself, whereas the amniotic cavity does not give rise to the embryo, but it forms a cavity that eventually comes to surround the embryo, providing it protection. So initially it sits above the bi-laminate disc, but it gradually elongates and extends and comes to surround the embryo.

By around day 40 or so it pretty much completely surrounds the embryo. Now that was one of the two cavities. What about the other one? So the amniotic cavities on top, bi-laminate disc, which becomes embryo. What about the yolk-sac? So the yolk-sack also grows, but it grows in a bit of a different way. Instead of growing to surround the embryo, it kind of elongates and pokes outwards. and eventually part of it sort of extends to the edge of the blastocyst cavity that it's within.

Remember that this whole thing is occurring within the blastocyst cavity. And eventually the parts of the yolk sac reach the edge of that and come into contact with the tissue of the mother. And this then gives rise to the umbilical cord. So part of what the yokesak does is give rise to the umbilical cord. So it forms the connection with the mother and becomes incorporated and is the umbilical cord. So before that happens, the yolk sac, its main purpose is a source of nutrients and a blood supply. So later on, as I said, as the embryo continues to grow, the yolk sac, I don't know if it actually shrinks, but it sort of becomes smaller and smaller relative to the embryo.

So the yolk sack is initially quite large. It's much larger than the bilaminar disc. But over time as that grows, the yolk sac becomes less evident. And most of it becomes, most of the tissue becomes incorporated into the umbilical cord. and parts of what were the yolk sac do become later incorporated into the gut of the embryo. So some of the yolk sac cells do become part of the embryo, but mostly the embryo comes from the cells of the bilamina disk. And I should also mention what happens to the tropeblast cells. So remember the trophoblast cells are the initial outer layer of cells that surrounded the blastocyst cavity and the inner cell mass.

So what happens to those? So these cells differentiate and develop into the outermost membrane of the protects the embryo called the Corion. It develops quite a complex structure, which I won't go into details of here. But the Corion basically protects the developing embryo. So there is then a layer of fluid. Inside of that we have the amniotic membrane which surrounds the amniotic cavities. That's another layer of fluid that serves all.

also is protection. And then we have the umbilical cord, which connects the placenta from the mother and provides nutrients to the growing embryo, and that develops from tissue that was originally the yolk sac. And then finally, at the innermost part, you have the growing embryo. So what makes this so complicated is that there are several membranes that surround and protect the embryo, and they all originate sort of at different times and from different types of tissue. So you've got the Corion around the outside, and then a layer of, and then a fluid-filled space. And then you've got the amniotic cavity with amniotic fluid inside that. And that's mostly water with some nutrients inside it, and that serves a protective purpose.

Then you've got the yolk sack, which provides initial nutrients, and it's also surrounded by a membrane. I've forgotten what its membrane is called, sorry, so that's a third membrane, and it eventually forms the umbilical cord. And then finally, at the center of all this, so surrounded by several membranes and protective fluid-filled sacks, you have the embryo itself. The embryo itself starts as sort of a flat disk, and then it gradually expands and kind of curves around a little bit. So for a while, the embryo, it looks a bit like a seahorse if you've seen an image of an early human embryo before. So it has a tail or at least what sort of is homologous to tails in organisms that. have them. It's sort of curved and then it has a region it will eventually become the head.

So it doesn't look very human-like for quite some time, but it gradually then develops its adult, or more adult-like form as it enlarges and elongates. So again, it all begins with the formation of the bi-laminer disk, which then enlarges, sort of curves around, you form sort of a swelling on one end, which will become the head and a sort of a tail at the other end, which will gradually sort of shrink away over the course of development. And then in the middle between those, like if you imagine the embryo is a sort of a sea shape, the head on one side and the tail on the other, the yolk sac extends out from the middle and then gradually the yolk sac becomes the umbilical cord. And so by around 40 days into development, we have this series of the

sort of concentric membranes with their fluid-filled sacks, the umbilical cord, and the early embryo, which is sort of curved and doesn't really look much like a human. You have very early limb buds that are forming at this stage, but they don't look very limb-like. What happens subsequently to that is that the embryo then becomes larger and larger, and the limbs become more clearly defined. The head develops, the eyes begin to develop, and the other components, like, for example, the umbilical cord become less pronounced, and they're still there. But essentially, the embryo and then later fetus becomes larger and larger relative to everything else,

and that the shape sort of becomes better defined. Now, there's one other process that I wanted to talk about, which is neuralation. This is extremely important, particularly for understanding vertebrates. So new relation refers to the process by which the neural tube is formed, and this will eventually give rise to the nervous system. We'll also understand here why it is that, remember the ectoderm tissue gives rise to the skin, well, that kind of makes sense, because the ectoderm arises from tissue that's on the outside, and the skin is on the outside.

But it also gives rise to the nervous system, and you might wonder, well, why is the nervous system also coming from the skin? Well, the process by which a new relation occurs makes this clear. So around day 16, so partway into gastrolation, mesoderm cells, so the mesoderm is formed by this point. Mesoderm cells just below the primitive streak. Remember the primitive streak that marked the beginning of gastrolation? So we've got cells that have migrated inwards, become mesodermal cells. Some of these cells, just below the primitive streak, begin to form a rod-like structure, and this will become what's called the Notocord.

The Notocord is a special structure, which is characteristic of all chordates. So chordates are essentially vertebrates plus a couple of other animals. It serves as a sort of a primitive axial, so extending from one into the other, endoskeleton, which is very important during the process of development. It sort of gives structure and support and anchors other processes. In most chordates, so an or vertebrate specifically, it is replaced by the vertebral column later in development. So adults don't have a notar chord, but they have a vertebral column which developed from the notic cord, but it's more of an embryonic structure. Now, the notar chord, as I said, begins to form during the process of gastrolation around day 16.

Gastrulation ends around day 19 or so. So about the time that gastrolation terminates, day 19 or 20, signals from the notor cord, begin to cause cells from the ectoderm, so that's the outermost layer of cells, to differentiate and form a thick, flat region called the neural plate. So the notocord is under the neural plate. The cells in the notocord send signals, cells in that region thicken up and form the neural plate. And then what we have is a process by which the neural plate folds in upon itself. It invaginates and then folds in, and then the tissue kind of pinches off. I sort of described this before. You have an enfolding, invagination, then the sides come together, they pinch off, and it separates out from the rest of the ectoderm, and it forms what's called the neural tube.

This process is fully completed by around day 28. And this neural tube is the initial basis of what will form the rest of the nervous system. So here we see why it is that the nervous system is, so originates from the same type of germinal layer as the skin, because it literally pockets off. from the skin. So it is sort of modified skin, but modified very early in the process of development. And so by day 40, we have the complete set of all of the major membranes that protect the embryo, so the corion, the amniotic membrane, and the membrane of the yolk sac, as well as the embryo itself. We've also had the neural tube forming. We have the three germinal layers, and now the embryo is is sort of ready to continue growing and the tissues further specializing into more specific roles.

Around this time, we have a process called organogenesis, which begins. This is the development of the different organs. So this occurs sort of roughly around the time we're talking about, roughly around the time of neurilation, and continues essentially until birth. Organs form through some of the same process that we've been talking about. So often what you'll have is something similar to the process of neuralation, right, where you'll have signals sent by one type of cell to other cells, which then begin to differentiate, thicken up, which then will either split off or it will invaninate and pinch off and form a

different organ. Another way that organs can form is through compensation of mesenchymal cells, so a bunch of sort of freely moving cells will come together and form a new structure. So these are the main ways new organs can form. They split off an existing membrane like sheet of cells, or they pinch off, invanionate and pinch off, or mesonogen. and kinal cells come and condense together. There are a number of cellular mechanisms and molecular mechanisms that mediate how this occurs. So one of them relates to cell-cell adhesion. So different types of cells express different surface receptors on their membranes, and this gives rise to preferential adhesion for some types of cells relative to others.

So if you have different types of cells in contact with each other, some of which adhere preferentially to, say, the same type of cells, then that can lead to these things separating out from each other or maybe adhering to each other in certain ways. So basically preferential adhesion of certain types of cells to others is one of these mechanisms that can help cells differentiate and migrate and shape in the ways that they need to. Another process is the cell matrix adhesion. The extracellular matrix consists of various molecules which adhere to the outer surface of cells and sort of connect them to each other. And the extracellular matrix can provide a scaffold that aids the migration of cells. So they sort of direct them where to go.

They follow along the extracellular matrix. There's also a process called chemotaxis. We discussed this before when we talked about how the sperm finds the egg, that it has receptors that are sensitive to progesterone. Well, that's an example of chemo-taxis, whereby cells move in the direction of a chemical gradient. And so they are able to preferentially develop or move in one direction, whether this is cells preferentially dividing in one direction, or whether it's mesoncomic cells actually physically moving in that direction,

if they express the right receptors. So only certain types of cells will be responsive to a certain type of chemotaxis because they express the right receptors. As these different cells to form different tissues differentiate, they become more specialized. And that happens by changes in gene expression. I've talked about this in previous episodes about particularly epigenetics. All of the cells in our body have the same set of genetic material, bar a couple of mutations, denobin mutations, but it's essentially the same DNA. However, they don't express all of the same proteins. The proteins that they express depend on very complicated patterns of inheritances that they've

received over the process of development and their mother cells and their grandmother cells and so forth going backwards over development. So certain genes will be turned on, certain ones will be turned off in very complex patterns, which will determine what that cell does. And once that differentiation has happened, there's no way to reverse that in the majority of cases. As she said, there are processes that have been developed more recently for basically turning cells back into what are called stem cells, which are more generalized, essentially, and then they can

differentiate into a wider range of different cells. We probably should do a whole episode on those, so I won't go into that here. But normally, what happens is that cells become more specialized and more differentiated over the course of development, which means they express certain genes, which result in them expressing the proteins that mean that they have the right type of receptors to be responsive to the right type of signals, adhere to the right neighboring cells, move to the right place in the body and engage in the right types of functions in order to do what they're supposed to do. Now, before we finish, I did want to discuss briefly some of the genetic mechanisms. I just mentioned some of the cellular and molecular mechanisms, but at the genetic side,

there's been some very interesting findings in the last few decades about some of the genetic mechanisms of development and connecting that to evolution. And this broad field linking development to evolution is sometimes called Evo-Devo. I don't really know why, but just in case you see that term, that sort of of what it's referring to. Now there's a type of gene or a collection of similar genes called hox genes. And these genes are found in, as far as I know, essentially all animals, or at least the vast majority of animals. And they are specialized for specifying regions of the body plan of an embryo along a tail-to-head axis. So there's like a linear positioning of these genes on a

chromosome. So these genes exist DNA that we carry on multiple chromosomes, but it is a linear sequence of nucleic acids. And so the genes are ordered linearly, one following the other. What's interesting is that these hox genes exist in clusters, which are linearly ordered. So they'll be like oxygen 1, hox gene 2, and hox gene 3, and they're in that order on the DNA. But what's fascinating is that the structures that they correspond to also exist in a linear ordering from head to tail along the body axis. So just to simplify, hox gene one might be the first one, and then there's hox gene two and hox gene three. Hox gene one might be expressed in cells that are in the head. Hox gene two might be expressed in cells that are in the neck.

Hox gene three might be expressed in cells that are in the lower chest and so forth, right? And this occurs not just in one animal, but it occurs in a wide range of different animals. So from insects and right through to humans. What it seems like is that these initial hoxen So I should say what the genes code for. A hox gene is defined by a short sequence of 180 base pairs, which is called the homeobox. And that's basically a conserved region. So they're all 180 base pairs long, which have a very similar, slightly different sequences between them. And these homeobox genes encode a DNA binding region, which is essentially where a transcription factor will bind.

And a transcription factor, if you recall, is a pro-tebrose. molecule or complex which binds to the DNA and affects its transcription. So whether or not that DNA will actively express a protein. So all of these hox genes have these similar homeobox regulatory regions which affect whether they are expressed or not. And in turn, all of these hox genes also express proteins which are transcription factors. So this is a little confusing. What I'm saying here is that these hoax genes produce proteins, they code for proteins, that are transcription factors, so they are regulatory proteins. And in turn, these hox genes also always have these hermobox regions,

which are regions that mean that they are regulated by transcription factors. So you can see how that can lead to very complex change of interaction, where you'll have, if you have a bunch of these hermobox genes, you'll have one gene that produces a transcription factor, which will affect the production of another transcription factor, which affects the production of another transcription factor, which may go back and affect the initial hox gene, or a different one, which then affects the first one,

which then affects the fifth one, which then affects the third one, which then affects the first one. And you see how it all becomes very complicated, and you can give rise to many, many different types of interactions in this way that can be modulated by the cellular context in the evolutionary, depending on the evolutionary pathway and so forth. So we find these genes in all forms of animals, or at least bilaterin animals.

So that includes all the protostomes and judo-stombs that we talked about before. And as I mentioned, there's also this interesting phenomenon whereby the linear ordering of these genes along the chromosome mirrors the regions of the body where the genes are expressed. So genes, again, the homeobox genes are found in every cell of the body, but they won't be active in all of those cells. And it seems that there's a linear relationship between where the gene is active, and where it sits on the chromosome, which is really interesting.

So what seems to have happened evolutionarily is that a very ancient ancestor had probably initially just a single hox gene, or a cluster, actually, they occurring clusters, but just to simplify, they had a single hox gene which then at some point duplicated. So now there are two, and then they duplicated again and again. And across evolutionary history, there was further duplication, and then mutation of the duplicated copies so that they then govern different parts of the body and then regulate different types of growth. So this seems to have begun very early in evolution because these hox genes are very highly conserved and they do similar things in different animals, but the

details are always different depending on the animal in question. So it seems that this is one of the major mechanisms that the body plans of animals have been regulated over evolutionary history is the evolution of these hoax genes. And the types of ways that this evolution can happen is effectively, you can change the protein product that is produced by the hox gene. So that occurs if you have a mutation in the protein coding sequence of the hox gene itself. So that will change its product, which will change what it buys to. Or you can have a mutation in the regulatory sequence of the hox gene. So that doesn't change the gene product, but it changes when that gene product is expressed.

So now it's expressed in different cells. So now those cells will become regulated in a different way to previously. you can also have changes in the post-transcriptional regulation and modifications of the hox gene, which can further affect what it does. So there's lots of different things that can happen to modify what these hox genes code for and how they are regulated, which in turn can affect how other things are regulated, and so it becomes a complex pattern. So it seems that this is a major process that has led to the differentiation of different body plans, and particularly appendages, body segments, major organs and things like that, in different types of

animals. It's these regulatory genes, not just the hox genes, but they're an important class of them, which are very evolutionary old, but have given rise to different body plans and specific patterns of tissue differentiation in different organisms. So that brings to a conclusion to what I wanted to talk about today. Obviously, I haven't gone through the full process of development in humans. I sort of ended it roughly at the sort of day 40 or so. But from there on, most of the major organs and types of tissues and the body plan has been laid down and development consists of continued growth and specialisation. And that's not what I wanted to predominantly focus on here. There's also kind of just less to say because it's sort of more of the same. So in a future episode,

I'll talk more about the reproductive system itself and I'll talk about like pregnancy and birth and those aspects that we didn't really get to here. But today I wanted to focus on the embryology side of things and talk about some of the underlying mechanisms and also similarities and differences between different types of animals because we'll be needing that information for when we go through the evolutionary history of life. So hopefully you found this interesting. If you would like to support the show, you can do so by giving a positive review on the wherever it is you get your podcasts. You can also go to a YouTube channel. So just to type Science of Everything podcast into YouTube and give some of our videos alike. If you've perhaps watched them, you can like them

on YouTube or you can share them with a friend, anything to support the effort to put the podcast on YouTube and get a bigger audience there. I'd really appreciate that. You could also support the podcast financially by making a one-off donation via PayPal to my email, Fodd12.gm.com, or you can become a Patreon supporter. I really appreciate all the support I've gotten on Patreon over the years, and that's really helped to fund, for example, work on bringing the podcast to YouTube and adding visuals to the audio. I am grateful for the support that's enabled that, and also all my editors for helping there. You can also send questions, suggestions, or other feedback to my email. As I mentioned, mods12 at gmail.com. Thanks very much for listening and I'll talk to you next time.