Lecturio Live – Session 3: Embryology with Dr. Peter Ward

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    00:00 Kate: Thank you all so much for joining this virtual event.

    00:03 Today we are going to be talking about embryology.

    00:06 We have our guest speaker with us Dr. Peter Ward, who I will introduce momentarily.

    00:13 This session is going to be recorded, and there will be a link sent to you by the end of the week.

    00:23 You know, with the recording, in case something happens with your connection, or if you have to leave early I know, for some, you know, for some people, in some places of the world, this is a very strange hour, possibly the middle of your night.

    00:36 So especially if you're joining us in the middle of the night or something, thank you so, so much for being here, we are very, very excited to talk to you today.

    00:47 All right, it looks like the chat slowing down a little bit.

    00:50 Um, yeah, so if you are having trouble hearing or seeing, at any point during this session, Obviously right now if you can't hear me, then I'm very, very sorry about that.

    01:04 My colleagues are posting in the chat how you can fix that so if anything, you know, ever happens, your connection goes funny, just refresh the page, make sure you have your other tabs, any downloads, everything closed, so that you have, you know the best connection you can have right here with us today.

    01:22 And if you're still having trouble, Google Chrome tends to be the browser that works best with the platform we're using today.

    01:32 So oh, wow, we've got someone tuning in from 3am, thank you so much.

    01:37 Good, very early morning, and yeah.

    01:43 All right, lots of different time zones.

    01:45 Alright, so we've introduced ourselves a little bit.

    01:50 So some of you have met me before, virtually or otherwise, my name is Kate.

    01:55 I'm the team lead for our student relations team, and we, you know, host all these events, so we host events, almost every month.

    02:03 We invite all of our Lecturio users, so if you're not already a user, definitely recommend at least creating a free account, and yeah, then you'll get invited to all of our future events.

    02:15 So, we just want to get an idea of who is joining us today, so who are you, where are you in your medical careers? You know, we have some people in our events who are at the very beginning, some people who are not even started yet, some people who are, you know, in different branches of medicine as some people who have been practicing for a long time, so just, you can answer that in the poll.

    02:39 So if you are on a computer that should pop up on the right side of your screen.

    02:42 If you are on your phone, that should pop up at the bottom, You might need to scroll down, and then you'll see our poll.

    02:48 So I see we're getting some answers in here.

    02:50 I'll give it a minute so we can kind of see the breakdown of who's joining us today.

    02:58 All right, looks like we have a lot of preclinical students and for the non students or others, who are you guys? What, what brought you in today? and yeah, you know, we've had all sorts of different people from different walks of life, very different careers, join us in events as well.

    03:18 So if you aren't, you know, not currently a med student, if you could let us know in the chat, who you are.

    03:27 We have a dietitian, we've got a resident, a molecular biologist, an electrical engineering student, pharmacy, pharmacology, science teacher, nurse, pediatrician, all right, we've got several biologists in here, big fan of medical health, embryologist, other medical students, high school students interested in medicine, well you are getting a very, very good headstart.

    03:56 Dr Ward: I see a couple of them.

    03:58 Kate: Yeah, Awesome.

    04:00 Anatomist, all right, cool.

    04:03 So thank you all, again, for joining us, and welcome to, you know, all of our students of life, who are here today as well.

    04:13 Second, and my last question to you, how familiar are you with Lecturio? So another poll is going to pop up.

    04:20 We just want to get an idea because I know we have people who are joining us who might not have ever heard of Lecturio, people who do know Lecturio.

    04:28 If you don't know what we're talking about, I will tell you in just a second.

    04:32 Go ahead and answer this in the poll, if you can see that.

    04:40 All right, we have a couple of premium members.

    04:43 Some folks watching our videos on YouTube, excellent.

    04:47 So I'm using the free version of Lecturio which is also of course available.

    04:57 All right, some have used it previously, but not anymore.

    05:00 Let's see if we can get have you back on back on track with us? All right, and of course, it looks like we've got some new folks.

    05:08 So bear with me for just a second.

    05:12 For those of you who are new, especially in those of you who might, you know, want to come back to us or need a refresher, here's just some information about Lecturio.

    05:19 So we are a learning science-based platform, the learning platform, we have everything from video lessons, 3d anatomy models, recall questions, Q bank questions, concept pages, a lot of different resources to support you in your medical studies and medical careers.

    05:38 And so this is learning platform.

    05:40 Our educator, Dr. Ward here is one of our wonderful, wonderful educators on the platform.

    05:46 And so there's just one specific aspect I want to tell you a little bit about.

    05:51 I'm going to come back to this at the very end and tell you a little more, but our concept pages are one of the coolest resources that I know of that exists out out there in the world.

    06:01 So these are like very much all in one resources about you know, different diseases, you know, different, just medical concepts in general, we have more than a thousand of them.

    06:14 And this is, you know, your all in one at your fingertips resource.

    06:18 So it's text-based, we have linked videos, there are other resources, different charts, illustrations, and you know, if you are a premium member with us, you can also access the related Q bank, so clinical case questions that go with these as well.

    06:32 And so just, this is one of the cool resources, and this is something that can actually be really helpful in studying embryology.

    06:39 So Dr. Ward will touch on that at the very end, when we tell you more about it, but I know some of you also come here looking for a deal.

    06:48 At the end, we are going to provide you with a special offer just for our event attendees.

    06:54 We do have, you know, a regular sale coming up because many of you might know, Thanksgiving is next week in the US, and that comes with Black Friday, which is a big shopping day, lots of discounts, lots of deals, but we're opening something up a little early for you so stick around to take advantage of that as well.

    07:12 But you don't want to hear from me anymore, who is this girl anyway, no one cares, I just want to introduce you to Dr. Peter Ward.

    07:19 He is a professor at the West Virginia School of Osteopathic Medicine.

    07:23 Now for those of you outside the US, you might be thinking osteopathic medicine, what? In the US, osteopathic doctors actually have the same practicing rights as you know, MDs, and so it's just another form of medical school here.

    07:39 And so it's Dr. Ward can maybe explain this a bit better than I can but you know, we have a very, very good educator and doctor on our hands today.

    07:49 He's going to talk to you about embryology.

    07:51 I'm going to stop talking so you can enjoy,and thank you again for joining us today Dr. Ward, please go ahead.

    07:56 Alright, thank you so much and yeah, wonderful introduction and I'm just amazed at the number of people and the variety of places you're coming from.

    08:04 Thank you so much for being here today.

    08:06 And if you have questions, be sure to enter them in the chat.

    08:09 We've got Shenika who is going to be monitoring the chat and getting the questions out to us.

    08:14 So today's topic, I decided to actually start with early development, the earliest part of development, starting with fertilization, and moving towards tissue differentiation, because I think it's important to get the very basics of the process down, and it's also one of the more complicated parts and in my experience teaching, this is a place where people tend to get lost, which is a shame because it sets up everything else that happens in embryology.

    08:40 So I always try to spend a bit of time and try to make things clear about what's happening at this stage.

    08:46 So with no further ado, let's see where it all begins.

    08:52 So early on, we have just an undifferentiated clump of cells, and as we pass through various weeks in stages, we can see as we move clockwise around this illustration, that we go from something that doesn't appear even to be animal-like to something that's vaguely animal-like with a tail, limbs head to something that we're going into the fetal period and we actually have a human looking organism, a new person has developed over that time.

    09:22 But what's happening between here and here is some complicated things for people to understand because we're not looking at a obvious body, we're looking at a clump of cells that is becoming a body.

    09:36 And so that's what we're going to be talking about today.

    09:40 So, early on, immediately following fertilization, which is a topic in and of itself, so I'm going to be skipping over fertilization in its details.

    09:50 We have the embryo at it's one cell stage, and then moving further along to become a zygote multicellular with multiple cells, and then we undergo the process called gastrulation.

    10:01 And we'll go to the point of gastrulation and we'll only be touching on a little bit of the sequence that follows that to set up the rest of the tissues of the body.

    10:12 So let's get going with fertilization in just a brief detail, not to the extreme detail that we go through in the entire course.

    10:21 So essentially, as soon as the spermatozoon penetrates the oocyte or the egg, it moves through the cells of the corona radiata, and then moves into the zona pellucida, which is a glycoprotein area around here surrounding the oocyte.

    10:38 And then the nuclear material from the spermatocytes and oocyte merge, and we get our first meiosis.

    10:48 Now that is going to set up our first instance of a new cell containing a new potential organism that is an individual.

    10:56 And so we go through the process of meiosis, and this single-celled zygote will split and undergo the usual process and we wind up with a new diploid organism, a new person.

    11:08 So the egg had had several activities on hold in terms of getting ready for eventual fertilization, and once the spermatozoa has joined it, it can continue dividing.

    11:20 And basically, about 30 hours after the initial fertilization, the zygote starts its division via mitosis.

    11:27 Remember, meiosis creates the germ cells, the sperm and the oocytes.

    11:32 Mitosis is the normal process of cell division, and we get two new and hopefully identical daughter cells.

    11:40 Now at this stage, we've changed the name to a morula, and one thing that's very aggravating about embryology, and I am just as aggravated by it as I'm sure you are, is that everything keeps changing its name.

    11:52 And if we can just keep track of what these things are, as they change their name, half of the difficulty is going to be explained.

    12:00 So we have the morula, splitting from one cell to two into four, and one important thing about this process is, it's not getting any larger, the divisions are happening, and we are getting more cells but each of these daughter cells is smaller than the original zygote.

    12:18 So by the time we reach the 16-cell stage, the morula, we've got a bunch of clustered little cells in here, and the zona pellucida surrounding it starts to break down.

    12:30 and fluid starts to trickle in, which is going to create a new form of the same structure called a blastocyst.

    12:37 It's all the same cells, but here the division keeps happening, fluid penetrates, and creates the blastocyst, which is going to be very similar, but with a cavity inside the entire organism.

    12:51 So let's jump in to a little bit of detail here.

    12:54 The morula, once again, is the same size as the zygote, and the cells within it are fairly uniform but at this stage, they start to differentiate.

    13:05 And at this point, we have an inner cell mass and an outer cell mass.

    13:11 The fluid that starts percolating through as the zona pellucida, this outer protective layer breaks down is going to start to make gaps or little cavities form in between the cells.

    13:23 So the zona pellucida is there and as the fluid moves in, it's going to create an offset cluster of what are called the inner cell mass.

    13:35 So we have inner cell mass cells right here, there are outer cells.

    13:40 Right here's the outer cell mass, it's forming a ring around it.

    13:44 And we have a cavity now.

    13:45 Now the same group of cells that we've been following all along, is now called a blastocyst, and this fluid filled cavity is called the blastocyst cavity.

    13:55 So we've moved forward from a single-celled zygote to a morula to a blastocyst, and all we've done is reorganize how these cells are clustered together.

    14:07 And the question in the chat is as division progresses, volume remains constant until the morula stage? Yes, at the blastocyst stage, you may be able to get a little bit of expansion as the cells and fluid are pushing outward, but from the zygote to the morula, we pretty much stay the same volume.

    14:25 Good question.

    14:27 So the blastocyst continues to develop as development and mitosis continue and we have at around five days, 107-stage cell of the blastocyst.

    14:39 And this is roughly 107.

    14:42 We've got an expanded blastocyst cavity there.

    14:46 And we're going to call this the late blastocyst.

    14:49 Now, the inner cell mass is going to change its name to become the 'embryoblast'.

    14:54 Once again, same thing but because embryologists had to justify their positions, we have slightly different names changing at different points.

    15:03 So we have the embryoblast coming from the inner cell mass, and the outer cell mass has become something called the 'trophoblast'.

    15:12 So the trophoblast is going to be what we refer to as the cells that are on the outside, and the blastocyst cavity or 'blastocele' is going to be the fluid-filled space in between there.

    15:24 Question in the chat, what is the earliest stage of embryogenesis that a teratogen would affect development of the embryo and fetus.

    15:31 Honestly, it could happen from the moment of conception on.

    15:34 If there is some sort of a toxic exposure, or teratogen present, it can disrupt formation of the cell.

    15:40 And then at any stage thereafter, you can have teratogens or chemicals or other signals that cause mutation disrupt the process of development.

    15:51 One thing thankfully, is that by the time we get to the fetal stage, most of the organ systems have formed, and exposure to teratogens after that might disrupt the structures that are formed, but won't necessarily affect their formation at all, because we've already got them formed, and growing and developing further.

    16:13 Alright, so we've got the trophoblast there.

    16:16 And we are going to more or less ignore the trophoblast from here on out.

    16:21 But here, I'm just going to recapitulate what we've already said, the morula's outer cell mass has become the blastocyst trophoblast, and we won't talk about it now but it's one of my favorite topics is how the trophoblast and its subdivisions become the placenta, and the umbilical cord that will actually take oxygen from maternal blood, supply the fetal blood with it, which then goes back to the umbilical cord.

    16:48 Instead, we are going to focus on how the morula's inner cell mass transitions to become the embryoblast of the blastocyst, and that becomes the actual embryo.

    17:01 There's a question about how these events occur and what signals control them? That is an excellent question, it's actually beyond my scope of knowledge.

    17:08 There are several genetic signals involved in the process, and there are several important ones like Sonic hedgehog, Wnt, and others, the Hox gene family, but I'm not able to discuss those in detail and I do bring some of them up in the full course, but that is an active area of research and I'm sadly can't give you a full explanation of every signal that's there, because we simply don't know all the signals that are happening at this stage.

    17:36 And one more question, can that process proceed even if there's an abnormality from the pituitary gland? At this stage, we don't have a pituitary gland.

    17:44 That's going to be coming in during the late embryonic period going into the eighth or ninth week as the central nervous system is developing.

    17:53 So it's really not going to be there.

    17:55 It's going to be more important as we get signals released during later development, and then during postnatal life outside the womb.

    18:05 Alright, so now let's jump here.

    18:10 So we've got day seven, and what's happening on day 7 is now we've got the blastocyst moving into the uterine lining.

    18:18 And those trophoblast cells are burrowing into the uterine lining and pulling the blastocyst into it.

    18:25 At this point, we still have our embryoblast here but because things have to keep changing, we now have a subdivision of the embryoblast.

    18:34 And in blue, we're showing the epiblast cells, and in yellow, showing the hypoblast cells.

    18:39 Oh, and there's been an explosion in questions.

    18:43 What is the difference between the embryo and the fetus? Essentially, that is going to be roughly the first 9 to 10 weeks of development will be the fetal period, and thereafter is going to be the.. pardon me I've messed that up.

    18:55 is going to be the embryonic period, and thereafter from the 9th or 10th week of development to birth is the fetal period.

    19:03 And the very short answer is the embryonic period is when all of the organ systems are forming from scratch.

    19:10 And in the fetal period, the organ systems have formed and now they're getting bigger, the body is expanding and growing inside the uterus.

    19:23 I believe the question is what is going to control the embryonic development? Essentially, the clock for embryonic development will be different signaling genes as alluded to earlier.

    19:35 Some things like the Hox genes will be involved in determining how many vertebra we have, when the limbs are going to form, but it's going to be intraembryonic signals that can be driven up in activity or depressed in activity by signals from the maternal bloodstream, as well as other hormones But essentially, intraembryonic signaling between cells will be what actually is controlling the process of development, along with just the continued proliferation of daughter cells in pregnancies, what stage.... (inaudible) Woof.

    20:12 And you guys are jumping into some of these tough questions already.

    20:15 In terms of twinning and twin pregnancies, in the overall course, that gets discussed in the placenta discussion because that's one way that you're able to actually determine whether or not twins are fraternal or identical.

    20:29 Essentially, at what point can you tell if they are identical or sorry, monochorionic or dichorionic? That's going to be in just a little bit.

    20:38 And if you have two separate blastocysts form in a single cell, you're going to have a monochorionic cell as a result.

    20:46 So yeah, that's actually going to be something we'd have to touch on in the overall course because I don't think I can answer all of that today and still make it through the presentation.

    20:55 But these are great questions, I'm sorry I can't actually hit them all in detail right now.

    21:01 And at what point in this process, is it possible for groups of cells from one zygote to form two organisms? That can actually happen multiple times.

    21:09 You can have a blastocyst develop two inner cell masses, and further on in the process, you can have it split and form to what are going to be called 'primitive streaks'.

    21:20 We'll see those in a minute.

    21:21 But it can actually happen over a period of time from the blastocyst up until the point where we actually have the three different germ layers of the embryo forming, which we'll talk about towards the end.

    21:32 And you guys are on top of your game, good job.

    21:35 So jumping back to the slide, we have the hypoblast and epiblast.

    21:41 The hypoblast is going to be the cell layer that's in contact with the blastocyst cavity, and these are going to expand out and coated.

    21:49 The epiblast layer is going to be the cells that actually create the rest of the embryo.

    21:55 So we've come all this way and we've still not gotten to the point where we're seeing only the cells that make the embryo until now, that's the epiblast.

    22:03 So epiblast there in blue will make the structures of the embryo.

    22:07 The hypoblast there in yellow is in contact with the blastocyst cavity, and we'll see in just a moment, it's going to expand and coat the entire cavity.

    22:15 Now at this point, we get yet another cavity coming into play, and we have cavities here in the amniotic area.

    22:23 This is the amniotic cavity in the epiblast region.

    22:26 Now, one thing that always bothered me when I learned this is why do we have all these cavities forming? What's the point? Why do we have fluid moving in? Well, the point is, we don't have a circulatory system yet.

    22:37 And the embryo, its cells are relying on simple diffusion to get gases, nutrients and wastes to and from the cells.

    22:45 So we really actually need fluid nearby so that we can actually have transport of the structures to the developing cells.

    22:52 So until we have a circulatory system, we have to have a sequence of cavities to actually allow these cells to continue dividing, and not get kind of clustered in concentrated waste that they're producing as a result of their mitotic activity.

    23:09 So we now have the endoderm lining the blastocyst cavity.

    23:15 Once that happens, yet again, it changes its name, it's called Heuser's membrane.

    23:20 And once it's completely coated, we call this new, well, not new, but this newly coated blastocyst cavity changes to become what's called the primitive or primary yolk sac.

    23:31 So again, we're changing something we've already seen to have a slightly different name, but the blastocyst cavity has become the primary yolk sac once those have surrounded it.

    23:43 We can see the amniotic cavity here as well.

    23:47 Now, this is a stage where something a little bit difficult to visualize happens, but I think we can cover it all right.

    23:54 We've got the blastocyst cavity, now primitive yolk sac here, we have the 'trophoblast cells' surrounding the developing embryo, then we have a new set of cells that are dividing and coming into existence between them, between the trophoblast and the yolk sac.

    24:12 These are called extraembryonic mesoderm cells.

    24:15 And meso- means middle, extraembryonic is giving you a clue that these actually don't contribute to the developing embryo directly, but are going to form support tissues for it.

    24:26 And as development proceeds, they get larger and larger and will eventually surround this area.

    24:33 And as things get larger and larger, just as we discussed a moment ago, there's going to be a cavity that forms and this extraembryonic mesoderm gets its own cavity, And that is going to be what is the 'chorionic cavity'.

    24:48 So this chorionic cavity is going to form around the developing embryo.

    24:53 We have the the endoderm and epiblasts - they are not the endoderm - the hypo blasts and epiblast cells here.

    25:03 And initially, the chorionic cavity is going to surround them, but eventually this little gap up here, that amniotic cavity, that is going to form the cavity that surrounds the entire embryo and contains the water that is going to be surrounding the developing fetus, and when someone's water breaks, that is going to be how it's actually surrounding the embryo, and when that membrane ruptures, the amnion comes outand helps the person to have the fetus delivered.

    25:34 So that chorionic cavity keeps expanding as the embryo enlarges.

    25:39 It's moved all the way into the uterus at this point, the extra embryonic mesoderm is in contact with the trophoblast cells here in development, or contact here with developing yolk sac.

    25:50 And now the yolk sac is also starting to divide, it's moving from being one big compartment into two.

    25:59 Now, I can't give you a definite answer on this as to why that's happening, but my my thought process on this is, I think, because we have fluid filled spaces, and fluid has a constant volume, it comes down to physics.

    26:13 And that as we get stretched here, and the volume doesn't expand, we're pulling this apart, as if there's a vacuum pulling one half of the embryo, and it's yolk sac away from its anchored point up here.

    26:26 But don't quote me on that, that's just my educated guess as to why we have that splitting happening at that point.

    26:33 But the primary yolk sac is splitting into two parts.

    26:37 And it's going to transition to become the definitive or sometimes secondary yolk sac, which looks about the same.

    26:44 And these exocoelomic cysts that are going to be on the opposite pole of the developing embryos.

    26:49 We have the chorionic cavity here, surrounding the developing embryo, yolk sac, a definite yolk sac here, and in other animals, it is indeed the yolk sac that's providing nutrients for the developing organism inside an egg, etc.

    27:05 And where we look and see those blue cells, that cavity in the blue cell is going to be the amniotic cavity, which doesn't look like much yet, but as I mentioned, it's going to expand tremendously.

    27:18 And see, I'll try to orient you all as we go through this.

    27:21 We're basically looking at this in terms of the spherical developing embryo in a cross section along its long axis.

    27:29 And I apologize that you can't see the cursor, that's just one of the particulars with this platform.

    27:37 Otherwise, it works really well, but the cursor would be a nice touch.

    27:42 So we're getting to the end of this initial stage of development.

    27:48 We're about two weeks in, and we have an embryo that is developing within a chorionic cavity,.

    27:54 It's connected to the trophoblast, which is shown in green, and the trophoblast will eventually become the placenta.

    28:01 There's a connecting stalk, holding it there.

    28:04 And if you can think about what a fetus looks like, shortly after birth, It's connected to the placenta by the umbilical cord.

    28:11 And the umbilical cord is going to develop from that connecting stalk.

    28:14 But what we don't have yet are any large vessels, because we're still relying on diffusion of nutrients and gases through the fluid of these compartments.

    28:26 So now we're moving on to gastrulation.

    28:30 And some embryologist like to say that this is the most important event of your life, and you weren't even aware that it was happening at the time.

    28:37 That's a little bit pessimistic, I like to think we haven't peaked until we're out of the womb.

    28:41 However, it's hard to argue with the importance of gastrulation because we're moving from that set of cells with a connecting stalk to something that looks relatively human.

    28:53 We're going to have a back and ahead and the caudal end and limbs by the time we're done with the process of gastrulation and a few of the steps that go past it.

    29:04 Now the first thing that happens -well pardon me, The main thing that happens in gastrulation, as we move from having these epiblast cells on top, and hypoblast cells below to having three different germ layers, and they're called the ectoderm, the mesoderm and endoderm.

    29:23 And we're going to actually have a chance to see how that happens here.

    29:27 So the bilaminar embryo, initially is just a cluster of cells, it's kind of disk shaped, but it becomes polarized as signals released in what will eventually be the head or cephalad portion of it are going to be formed what's called the prechordal plate which you can see on the left side of the image.

    29:45 That's going to mark the eventual formation of where the head and mouth are going to be.

    29:50 And on the opposite side towards where we're going to have the tail-like or caudal region, we have what's called the primitive streak.

    29:59 Now the cells in this region are forming a crease that allows cells to migrate deep to them and towards the underlying hypoblast.

    30:09 And at the very tip of it, we have something called the primitive pit, where we have the final kind of end of it.

    30:16 And the primitive node is an important signaling area releasing lots of important signals.

    30:20 One of them is called 'nodal' in this area that allows the body to differentiate between its right and left sides.

    30:26 Now, this process of involuting through the primitive streak is one of the places where people tend to struggle.

    30:34 What I want you to remember is all these cells are still proliferating.

    30:38 They're still undergoing mitosis, and we still are making cells.

    30:42 What's happening is these epiblast cells are moving through the primitive streak, and pushing down underneath it to create new layers.

    30:51 There's going to be a mesodermal layer forming below it, and an endodermal layer forming below that.

    30:56 But because using those words doesn't really convey anything, I've got a quick and hopefully, you know, low budget explanation here - thank you for shifting.

    31:06 So if we think of my nice blue gloves here being the epiblast layer of the cells, so let's just say this is me, here's my front side where the hypoblast would have been, back where the epiblast would be.

    31:20 If these cells are laid out this way, and they form the primitive streak, the cells are involuting, they're making a little valley.

    31:28 And as the cells keep proliferating, they get pushed into this valley and as they go, they're going to take up space deep here, and as they do that, and move in, they leave cells on the top, they're going to be the ectoderm.

    31:42 And then we're going to have the mesoderm and endoderm below there.

    31:47 So you go back to the slide view now.

    31:50 And hopefully that will make some of this a little more sensible as we go through it.

    31:55 So these migrating epiblast cells are going to utterly replace, at least in humans the hypoblast layer, and the epiblast will make the ectoderm, endoderm and mesoderm.

    32:09 Now as this is happening, we're going to have these cells migrating through different regions of the primitive streak.

    32:17 At this point, the ones that are very close to the node, the very front part of the primitive streak will migrate directly forward and they're going to form a notochordal process and eventually an important signaling structure called the 'notochord', and it's going towards that three quarter plate, which has now surprise, surprise, change names, and is now called the oropharyngeal membrane.

    32:40 The oropharyngeal membrane is an important area because it's one place where ectoderm on top and endoderm below are in direct contact with each other, and there's no mesoderm in between.

    32:51 And they kind of form a little bit of a pinch point that way.

    32:54 Likewise, on the far end of the primitive streak, we have a cloacal membrane where the ectoderm and endoderm are met together there forming a thin membrane.

    33:05 Now as the cells migrate through the primitive streak, the ones that are just a bit lateral to the primitive node, instead of making the notochord are going to be traveling a little more laterally.

    33:18 And as you go further back, if you look on the right side of the illustration, they're going to be forming other structures as they go further and further back, forming more and more laterally as they move through.

    33:29 So here, we're now taking a cut through this section so if you think about us taking a slice right through the middle of this image, that's basically what we're looking at here.

    33:40 We have the mesoderm shown in red, the endoderm shown in yellow, and the ectoderm shown in blue.

    33:50 We can see the oropharyngeal membrane on the left, and the cloacal membrane, the two places where the blue and yellow directly touch on the right.

    33:58 The notochordal process snakes underneath the primitive node, right where it's going down the midline of the body.

    34:07 And as we travel a little further along, that process forms an actual circular cluster of cells called the notochord.

    34:14 Now, the notochord is a very important signaling molecule, a primary signaling structure that releases molecules that are going to allow different things to happen in the formation of the muscles, the bones and the central nervous system.

    34:27 In humans, at least it only retains itself in little bits of our intervertebral discs, the nucleus pulposus, but it's important early on.

    34:37 And we've got some questions that have cropped up while I've been talking.

    34:41 Let me see if I can catch those.

    34:43 Who will give command to the zygote to differentiate particular cells of the body? I can't actually give you a "who" on that one, I think that that's delving more into theology and religion.

    34:55 However, I'd say that essentially the signals that have been on hold in the egg, and the nuclear signals that are released from the cell and its continued division are going to be what drive the internal formation of the structure from there.

    35:10 So I think we got that.

    35:12 Next up, what is the difference between the mesoderm and endoderm? Great question.

    35:17 This picture is showing the difference, the endoderm is in yellow.

    35:22 It's the area that's in contact with the yolk sac, whereas the mesoderm means middle skin or middle flesh, it's actually the the red part.

    35:31 And it's in between the blue ectoderm and the yellow endoderm.

    35:36 And what else do we have here? Why is it that the intraembryonic coelom splits the mesoderm into somatic, oh, that actually is going to happen in just a little bit, we haven't gotten to that spot yet where the smeda floor and the split Gnuplot form, so I'm going to kind of ask you to lay that Ellen, but we will get there. Alright, so What's happening is we now have the ectoderm in blue, and we're starting to get these cells to become more columnar, they're growing upward, especially on either side of where the notochord is.

    36:08 The notochord is part of the mesoderm.

    36:10 It's here in this pinkish red, and it's going to start forming a tube.

    36:16 And this is going to happen a couple times, but essentially, the tube forms because it grows upward, involutes, and then just pinches itself off, and moves fully into the mesoderm.

    36:25 And it's going to bring the two edges of that endoderm together on either side.

    36:30 And so when that's done, instead of a notochordal plate, we have an actual notochord here.

    36:36 Now at this point, if you looked at this, you might be forgiven for thinking that the notochord is going to make the spinal cord and central nervous system.

    36:44 It's not, but it's in a very similar position.

    36:48 What's going to make the central nervous system are those ectodermal cells that are located above it.

    36:54 And one of the stranger things about human development or any vertebrate development for that matter, is that the same cells that make the outer layer of our skin, the epidermis, also make our central nervous system our spinal cord, our brain and our brainstem.

    37:09 And just a quick aside, one of the strangest things I've ever seen in the anatomy lab was a brain that had hair inside a cavity within it.

    37:18 So some of the cells that were presumptive skin cells got included with the folding of the brain.

    37:24 So that's one of the strangest things I've ever seen there.

    37:28 The notochord is what's causing this development to occur where these cells are growing, and we have a neural fold on either side of the ectoderm.

    37:37 Meanwhile, the mesoderm is starting to differentiate into what's called paraxial mesoderm and mesoderm that's a little further away, intermediate mesoderm.

    37:45 And to the far left, and far right there is lateral mesoderm, also known as lateral plate mesoderm.

    37:52 So that red intraembryonic mesoderm, the stuff that's pinched between the ectoderm and endoderm is going to form a great many of the structures in our body.

    38:03 So as the mesoderm passes through the primitive streak, its fate is going to be determined by where it passes along.

    38:10 If it's going along the exact midline towards the pharyngeal membrane, it becomes part of the notochord.

    38:16 If it passes a bit more laterally, it's gonna become cardiogenic mesoderm attributing to the heart.

    38:21 And then if we go even further caudally we're going to form paraxial, very far lateral intermediate, And then sorry, I misspoke.

    38:31 paraxial, close to the midline, then intermediate, and then the lateral mesoderm, or lateral plate mesoderm.

    38:38 And that's in contact with the extraembryonic mesoderm on the outside of the embryo, which supports it, but doesn't actually create anything in the body itself.

    38:48 Alright, so I've been moving along at a decent clip, but we'll have to pick it up just a little.

    38:53 So we'll see if we can get all the way through in the time we've got.

    38:56 Now the neural tube is going to be what forms the structure of the central nervous system.

    39:03 So if you look just above the notochord, in the center of this image, you can see that there's a groove or a little depression, and there are little elevations on either side of it.

    39:13 There's going to be a neural groove right there and we're going to have growing of those cells on either side of it.

    39:20 The mesoderm, we have paraxial, intermediate and lateral plate mesoderm nearby as well.

    39:26 And as the structures continue different, what's going to happen is the ectoderm is going to make the outer skin and central nervous system, the endoderm is going to make the lining of our body cavities.

    39:37 So the gut lining of the gut to respiratory tract, urogenital tract and the mesoderm is going to make almost literally everything else.

    39:47 So the mesoderm is vitally important because it's making so many things in the body.

    39:53 So tracking what happens with the paraxial mesoderm, the stuff that's closest to the notochord then the intermediate and lateral plate mesoderm are a whole set of instructions or a whole set of lectures that we have available as well.

    40:06 But it's important to remember that the notochord is what's releasing the signals that are driving a lot of this activity, as well as the signals that are released by the tissues to communicate with the notochord and complement them and maintain the signaling processes.

    42:26 As that's happening, it happens initially at the very center of the embryo.

    42:31 It doesn't happen simultaneously, all along the entire length of the embryo.

    42:35 So if you look at the left side, you can see that the neural grooves are approaching each other, that's those two blue streaks right down the middle.

    42:43 And on the picture on the right, you can see that they've gotten closer and the neural tube has invaded the body.

    42:50 And it's going to start pinching off completely from the overlying ectoderm.

    42:54 Now as that's happening, some little bulbous form, bits of paraxial mesoderm are starting to expand to the point that they become very, very pronounced on either side of the body.

    43:07 So as the neural tube invades the mesoderm, the paraxial mesoderm starts from indistinct somites and those are going to be structures that are very important for tracking the development of the body.

    43:18 I see someone mentioned in the chat neural crest are sometimes called the fourth germ layer, and I have a hard time disagreeing with that, they're fascinating cells.

    43:26 So the initial zipping together of the ectoderm is going to happen in the midline of the body.

    43:33 And that leaves a small portion of it open in the cranial part of the body called the 'cranial neuropore' and a small portion posteriorly called the 'caudal neuropore' that are still open to the amnion in the amniotic fluid.

    43:46 As the body continues zipping itself shut, we have somites flanking it on either side, and eventually we're left with the image on the right, a cranial neuropore that will close as the body completely separates from its amniotic layer, and the caudal neuropore that will close, more close to the tail end as possible.

    44:06 And we've got more and more somites forming along the length of the embryo as this occurs.

    44:12 So these somites are going to have a very distinctive pattern, and we're going to have four occipital somites, eight cervical 12, thoracic, five lumbar, five sacral, and several coccygeal somites.

    44:25 And for those of you who know your anatomy, you'll know that this corresponds to many of the nervous, the spinal nerves coming from those areas of the spinal cord, the somites and the division of the spinal cord, and the nerves that come from it are very intimately connected.

    44:42 Now, someone asked about neural tube defects, and yes, this is exactly where problems with neural tube defects can happen.

    44:49 So if you have a failure of the cranial neuropore to close on its appropriate time, you can wind up with birth defects that are similar to, that are basically a cyst projecting from the back of the skull because you have a failure of that mesoderm and bone to form there.

    45:08 More frequently, you can have the caudal neuropore not close in time, which will not allow the bones of the spine to form particularly the most posterior part of the spinous processes, and that can result in a variety of forms of spina bifida.

    45:23 And again, there are multiple forms depending on how severe that defect is.

    45:28 And we can get to that in the main course because we go into the different stages at which that can occur.

    45:34 Let's see, question, are neural crest cells a derivative of ectoderm? Yes, they are.

    45:38 So neural crest cells are derived from ectoderm.

    45:42 And good, I think we've got everything so far.

    45:46 So let's keep on rocketing ahead with the mesoderm.

    45:49 Now the mesoderm flanking the notochord and the developing neural tube is called paraxial mesoderm.

    45:56 And yet again, it's going to change its name to become defined, discrete somites which are visible bumps on either side of the developing embryo.

    46:07 In the head and neck, you can actually have things that are similar to them, but they don't form discrete bumps so they're called somitomeres rather than somites.

    46:15 So, the somites are going to form on either side of the neural tube, and they're going to contribute to a lot of the support tissues that are related to the neural tube in our eventual spinal cord.

    46:27 Let's see, how do teratogens affect the formation of the neural tube? Some of them very severely, I think, that's one thing folic acid is very good at is preventing neural tube defects.

    46:39 If cells are proliferating quickly enough to form the neural tube and allow it to actually shut you can wind up with those problems.

    46:45 So I think folic acid is one that you want to have very good intake for someone suspected that they're pregnant or is hoping to become pregnant.

    46:54 And okay.

    46:57 So right here, the somites will then split into different areas, and their names tell you more or less what they're going to form.

    47:05 The dermatome will become the dermal layer of skin, which will be in contact with the overlying ectoderm which forms the epidermis.

    47:12 The myotome, myo- is going to form muscles.

    47:15 And the sclerotome is going to form the vertebral bodies, the rest of the vertebra and some of the ribs, as well as the support tissues like the meninges, and so forth.

    47:26 So sclero- means hard, so it's going to form the harder structures, the cartilage, and eventual bone of the spinal column.

    47:33 So this is just showing that there's different differentiating regions of the sclerotome.

    47:37 We'll zip through this a little quickly in the interest of time, but the sclerotome will form a very loose approximation of the eventual vertebra here, whereas the dermatome and myotome on the outside will form the eventual skin, its inner vascular layer, the dermis, and the myotome for many of the muscles that surround and support the developing back in vertebra.

    48:03 Yes, I will zip through that little bit quickly.

    48:06 Just be aware, the meninges are also coming from this layer, the supporting tissues of the spinal cord and brain are coming from the sclerotome.

    48:14 Now, I can do this part quickly because doing it with any kind of detail requires multiple lectures, the intermediate mesoderm, just lateral to the somites, and coming from the paraxial mesoderm, it forms the kidneys, the ovaries, the testes, as well as their support ducts and tissues.

    48:32 And that's really all I'm going to say about it for right now.

    48:36 Now the last and not least thing that happens here and I'll try to finish this up relatively quickly is that we have, furthest most of the outside, the lateral plate mesoderm.

    48:48 And what's important about the lateral plate mesoderm is it's the area that lets us go from being this stacked, three layer sandwich of cells to become an actual, you know, vertebrate with an actual body wall.

    49:01 We're actually moving away from just a stack layer of cells to what actually looks like an organism.

    49:06 And the reason that happens is because there are gaps once again, fluid-filled gaps develop in these layers.

    49:15 This is called the intraembryonic coelom and believe it or not, that cleft is going to form our peritoneal, pericardial and eventually pleural cavities.

    49:25 That is going to become all the body cavities in the human body.

    49:29 But right now it doesn't look like much.

    49:32 What happens is that those clefts form, the intraembryonic coelom gets bigger and bigger and pretty soon we have mesoderm stuck to the ectoderm, and mesoderm stuck to the endoderm.

    49:45 The mesoderm in red that's in contact with the blue ectoderm is called the somatopleure and the mesoderm that's in contact with the yellow hypoblast cells, or not hypoblast anymore - the endoderm is called the splanchnic floor.

    50:00 And here, we're going to do this very quickly but what I want you to visualize here is that that space between them starts to get narrower, and the somatopleure expands out laterally and anteriorly to come together on the midline.

    50:17 And as it does so, it brings that into embryonic coelom and surrounds the developing gut tube, pinches it off, and forms a complete body wall.

    50:27 Now, let me just jump ahead real quick here.

    50:31 That's always a difficult thing to visualize, so we've got one last little in-person demo.

    50:36 I'm going to take this pink blanket, do my best to emulate the picture on the screen.

    50:40 If you imagine that my arms are the somatopleure, and that this pink blanket is the ectoderm.

    50:46 Sorry, I don't have a blue blanket, didn't have time to grab that.

    50:50 As it expands outward, it wraps around and makes a tube that surrounds the whole body, bringing everything together here, so that the space that was in front of the somatopleure intraembryonic coelom has now become my body cavity, right there.

    51:08 Alright, and go back.

    51:10 Let me go back to the slides and we'll hit the final streak here.

    51:15 So endoderm, I mentioned already becomes the lining of the gut tube, the respiratory tract and the urogenital tract.

    51:22 And all we have to really worry about initially is the gut tube, because the respiratory and urogenital tracts develop off of it.

    51:30 As the body wall is expanding, the splanchnopeure the area in contact with the mesoderm, and the endoderm is going to also roll closer together and pinch off to form a gut tube.

    51:43 So as it gets surrounded by the intraembryonic coelom, you have the embryonic cavity, it's going to pinch off a narrow gut tube, which remains attached to the yolk sac to a small structure called the vitelline duct.

    51:57 And meanwhile, the body wall is fusing anterior to it.

    52:02 And we wind up with a gut tube suspended from the body wall by a dorsal mesentery, and from the anterior body wall by a ventral mesentery.

    52:11 Now, if you think about your anatomy, the ventral mesentery, the only place it remains in the adult is the falciform ligament of the liver.

    52:19 Everywhere else, that goes away, and the gut tube is suspended from the body wall by a dorsal mesentery.

    52:25 That mesentery is important because that gut tube needs to have blood and innervation.

    52:31 And so all of its blood is coming from the aorta, which is developed in the mesoderm.

    52:37 Te visceral layer of mesoderm, just posterior to it, we have the developing gonads and kidneys lateral to that from the intermediate mesoderm.

    52:47 And essentially, we've got the gut tube forming that way, and we've made the most basic setup of the body that we have from that point.

    52:56 Now I'm going to leave it at that and we will just say that the same sort of things happening more further towards the head but there's going to be another layer that brings the fusing endocardial tubes together to form the heart.

    53:10 Because by the time we hit around day 22 and remember, this is about three weeks worth of development, all this stuff has happened in that time, we've reached a point where the embryo was too big for simple diffusion to occur anymore to do the job.

    53:23 So we've moved by the time we've gotten to about 22 days to become an organism that really does need a circulatory system in order to continue developing because diffusion will no longer take care of the business.

    53:37 And that is the point where we've got a head, a heart, limbs, a back, and we can basically follow the formation of any body system from there.

    53:47 And that's what we talk about in every one of the lectures in the large overall course.

    53:52 So I appreciate everyone's patience, this went a little bit longer than anticipated.

    53:56 But I will mention right now, that embryology is tough and it's a struggle for me to keep all the terms right every single time I speak.

    54:05 And as you've noticed, we have to kind of continually check ourselves to see what we're saying.

    54:10 One way to make sure that you master something is not to go at it the same way over and over and over because you get diminishing returns, it's to look at it in a different way.

    54:19 And I promise I'm not being a shill for the concept pages.

    54:24 I really liked them because they take the same material and put it in a slightly different context and allow you to look at it from a different point of view.

    54:32 And that's what brings about mastery of the material.

    54:34 So I appreciate everyone sticking around and I really appreciate your questions and your engagement in the process and thank you so much and I will turn it back over to our pals at Lecturio.

    54:44 Kate: Alright well, thank you so much, this was such an interesting session.

    54:47 I feel like I'm an expert now.

    54:50 Of course I'm probably not but Dr. Ward: I don't feel like I'm an expert so I don't know what to tell you.

    54:56 Kate: Yeah, so we are so you know, happy that all of you were here today.

    55:01 We've had a lot of great questions in the chat, a lot of them have already been answered.

    55:05 You know, as Dr. Ward said, these concept pages are here.

    55:09 One of my colleagues is going to share a link to a concept page in the chat right now, which will actually help you with today's lecture.

    55:18 So, we will keep, keep sharing some of those.

    55:21 As I mentioned at the beginning, we do also have a special deal for you.

    55:26 Soyou know, our, like, Black Friday deal week thing is coming up next week but we're opening this up early for all of you just for our event attendees, because you know, you're here and you're spending time with us, especially those of you for whom it's like 3 o'clock, 4o'clock in the morning.

    55:42 So this is an opportunity, we had a couple questions about pricing.

    55:48 We have a subscription model, the different plans are on that link, that should have just popped up here.

    55:54 One of my colleagues will also put that in the chat for you just for ease of access.

    56:00 I'm going to go ahead and say since we are almost out of time, Dr. Ward, do you want to answer maybe just two questions? Dr Ward: Are there any, I couldn't see any that jumped up? Kate: We do have some more, Shenika, can you maybe pop something up for us.

    56:17 so that we can see some of the good ones, I know, we answered a lot of them.

    56:24 Let me see.

    56:25 Dr. Ward: So real quick, I just want to also thank everybody, especially those of you who are tuning in, in the middle of the night, I hope it was worth staying up for.

    56:32 And I really appreciate all the kind things that you guys are saying in the chat.

    56:35 It's, I love talking about this stuff and I'm just happy there are people too, who are interested in hearing about it as well.

    56:41 Can you recommend any good books for embryology? There are many, the two that are usually the most applicable to medical students at the level you want with good clinical correlations are going to be more, Sorry, Moore and Persaud, The Developing Human and Sadler's Embryology, Those are two of the common ones that are taught in a lot of medical schools, because they have a lot of clinical correlations as well.

    57:07 Carlson's is a really nice embryology textbook as well.

    57:11 It isn't as clinical but it goes into more depth of the actual process.

    57:15 And then there are textbooks specifically about the genetics and signaling molecules that are involved.

    57:21 And as I mentioned, my focus is on the morphology, the change in structure, although the signaling molecules are obviously what's behind that, but if that's something that you really want to investigate, there are handouts, or probably there are textbooks specifically about the genetics related to it.

    57:37 So honestly, I just say go to a medical school, library and the internet, see if you can find any sample chapters to look at and see which ones actually look to be the most applicable to you.

    57:50 And I hope that goes well.

    57:54 Kate: All right, well, thank you so much.

    57:55 We've actually answered most of the other super relevant questions so I just have the last one for you.

    58:00 Could you tell us what other things you might learn if you check out the material embryology course? Dr. Ward: Oh, so, one thing that I loved about the Lecturio embryology course, being able to put it together is I learned a great deal about embryology.

    58:15 So, the more you study it, the more it kind of comes together.

    58:19 And for those of you who were still slightly confused by the end of today's quick talk, please don't worry, it's not simple, but one great thing about the embryology course, is that it always refers back to these initial stages to the endoderm, the mesoderm, and the ectoderm, because they're involved in the formation of multiple organ systems.

    58:40 So you can start with the same material and go different ways, depending on what organ system you're in, and really just seen how the embryo comes together.

    58:49 The, to make it sensible, we have to break it down into different systems but the really amazing thing to me is all of its happening simultaneously.

    58:58 And, you know, maybe someday before I retire, I'll be able to put together in my head, all of those things simultaneously happening at once. But right now, like the rest of us mortals, I have to break it into understandable chunks to really understand.

    59:14 Kate: All right, well, thank you so much.

    59:16 I just tried to share my screen so you could see, you know, in the Lecturio platform, what the embryology course looks like, there were some of the topics listed there as well.

    59:25 So again, Dr. Ward, thank you so much for taking the time today.

    59:29 Thank you all so much for joining us.

    59:31 If, you know, we might have missed a question here or there, please shoot us an email at

    59:38 One of my colleagues will put that in the chat.

    59:40 And you know, we will do our best to answer any follow up questions that you have.

    59:46 If you know if there's anything else, anything you want to see for future events, you're always welcome to send us some feedback.

    59:53 We love hearing from you, we hope you had a very, very good time today at our embryology event.

    59:59 We do these events about once a month, and so how do I get an invitation? and how do I know when the next one's coming? Join Lecturio.

    1:00:07 We send out invitations everyone, even if you have a free account, or you know, of course, a premium account is awesome.

    1:00:14 But you know, we send this out to everyone so go ahead to Lecturio, create your account or log in, just make sure everything's active.

    1:00:23 You know, maybe try a couple Qbank questions, check out some of our other embryology videos.

    1:00:28 And, you know, we'll see you at our next event.

    1:00:32 So, have a wonderful day, or night or morning or whatever time it is for you.

    1:00:37 And Dr. Ward again, thank you so, so much, and we look forward to next time.

    1:00:41 Dr. Ward: Thank you all very much.

    1:00:43 I appreciate everybody's hard work at Lecturio and especially everybody who tuned in to listen and participate, thank you so much.

    1:00:50 Kate: Alrighty, and for those of you asking about the recording, we will send around a link by the end of this week to you.

    1:00:57 So check your emails again, the same email you used to register here.

    1:01:01 So all right, we will see you then.

    1:01:02 Bye, everyone.

    About the Lecture

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