hi ninja nerds in this video today we are going to be talking about the development of the skeletal system before we get started on this video please continue to support us by hitting that like button commenting down in the comment section and please subscribe also down in the description box we have a link to all of our social media platforms you guys can go check that out and if you guys can donate patreon we would truly appreciate it all right ninja nerds let's get into it all right ninja nurse when we talk about the development of the skeletal system we're gonna have to have two primary goals throughout this video first thing is we've got to develop the axial skeleton so what does that consist of we've got to talk about the development of the skull okay and we'll talk about what's called the neurocranium and the visceral cranium in a second after we talk about the development of the skull then what we're going to do is we're going to talk about kind of the development of the actual thoracic cage right particularly the ribs the vertebrae and the sternum and then we'll finish up talking about the development of the upper limbs and lower limbs okay so let's go ahead and start talking about the skull so the first thing that we have to understand is is we're going to take which layer to make the skull do you guys remember from the videos that we've been doing here remember the mesoderm and the neural crest cells those are very important for developing some of the structures of the skull the first one that we're going to talk about is what's called the neurocranium the neurocranium is the part of the skull that encases or surrounds the brain so where does the neurocranium which we're going to talk about here so the first one that we're going to discuss is the development of the neuro cranium the neurocranium is going to develop from what structures well here we've got to take our tri-laminar disc from the triliminer disc what is it made up of i know you guys remember this the top layer is going to be the ectoderm the middle layer is going to be consisting of the mesoderm and we have all the different components of that mesoderm like the different subsets and we'll talk about those and then the last one that we said the most inner layer here is going to be the endoderm now kind of center axial right in the center of the mesoderm you have a couple structures you have this purple structure here what is that called this guy is called your neural tube it's called your neural tube and then you have the notochord this little like black dot that's going to be anterior to the neural tube or just above the endoderm then on the sides here what is this particular part of the mesoderm called that's called your par axial mesoderm that's very very important we'll talk about that in a second and then on the sides of the neural tube on the top what do you have the neural crest cells now here's what i want you to do we're only looking at a cross section of the embryo what i want us to do now is take this neural tube and just yank it out okay so i'm going to take the neural tube and i'm going to yank it out and i'm going to smack it right there then i'm going to take the neural crest cells which are on the sides of the neural tube and i'm going to yank those out and put those on the sides then i'm going to take these chunks of par-axial music and yank those out and put those on the sides now let's talk about these things so first thing we have here is our neural tube we're just starting to see the vesiculation here don't worry about that yet but what we have on the side of the neural tube is these little brown dots what are these little brown dots here called on the side of the neural tube this is called your neural crest cells these are called general crest cells and these are going to be towards the top of the actual neural tube then these red structures here which we said was particularly what the par axial mesoderm this is called your par axial mesoderm remember we talked about in the mesoderm video the par axial mesoderm undergoes this kind of segmentation process where it forms somites well the somites that are up towards the top right are actually what type of somites occipital somites so the particular part of the paraxial mesoderm that we really need to know is called the occipital somites what are those again you have a chunk of mesoderm par axial they start segmenting making somites the ones towards the top are occipital somites if we take the neural crest cells and the occipital somites and combine them together guess what we get the neurocranium so what these things start doing is these cells start migrating around the skull and they start making a bony covering around the actual brain and what is that called your neurocranium now we got to talk about the tops of the parts of the neurocranium so you have the base of the neural cranium there's a very very important name for this the base of the neural cranium what we're doing is is i'm chopping the skull like this i'm chopping it looking into the skull and what i see is i see a couple different fossas if you will this right here is called your posterior fossa this one here is called your middle cranial fossils you've got posterior cranial fossa middle cranial fossa anterior cranial fossa there's a bunch of bones that make up this base of the skull what are those bones you have the occipital bone what else do you got you see this kind of bony part here that goes like this this is called your petrous part of the temporal bone what is this called this is called the petrous part of the temporal bone all right so we got two bones so far we got the occipital bone and then we got the petrous part of the temporal bone then you have this bone right here all of these bones that are kind of coming off of this point here and moving outwards this kind of gives like a bat like appearance it will kind of extend from here to here all this in between this is called the sphenoid bone so this is called your sphenoid bone and then last but not least you have this bone here right in the front this little kind of like thing coming up called the crista golly but this whole bone here is called your ethmoid bone these bones are what make up the base of the skull and are part of the neurocranium here's what's very interesting though this is what's very important this neurocranium is also given another type of sub name if you will and the sub name for it is called the chondrocranium the reason why i want you to remember that is chondro means cartilage so chondrocytes what we have is the par axial mesoderm and we have those neural crest cells technically these are these become what's called multi-potent mesenchymal cells and these mesenchymal cells undergo a specific type of process where they differentiate and when they differentiate they turn into a special type of cell called a chondrocyte okay so we got our mesenchymal cells that turn into a chondrocyte then what happens is this chondrocytes create the framework and then start actually differentiating into what bone so then your chondrocytes start converting into what's called bone particularly what's called osteoblasts this process where you go from mesenchymal cells to chondrocytes to osteoblasts is called what endochondral ossification so this is called endochondral ossification endochondral ossification is important because most of the bones are developed most of our skeletal system is developed by this process very important to remember especially the chondrocranium component of the neurocranium the other type is this here we've only talked about the basis goal remember i told you i took a section like this and i looked into the actual skull cavity well that part that i cut right here the part that i'm removing the calvaria that right there is going to be this part that we're staring at this comport component here is also a part of the neurocranium but again we got to give it a special little name so we call this one the chondrocranium the base of the skull the top of the skull is actually going to be called something very interesting this one is called the membranous neurocranium the membranous neurone this is the chondrocranium or the chondro neurocranium and this is the membranous neurocranium so what kind of process do you think these actual uh cells here what kind of cells the par axial mesoderm which part though the occipital somites and the neural crest cells they go a differentiation process but this time guess what they do they convert straight from the mesenchymal cells to bone tissue osteoblasts and then start making bone this process here is called intramembranous intra membranous ossification intra-membranous ossification and not many bones in the body are developed by this process one of the few is the top of the skull now what bones make up this and then one last thing that we got to talk about the bones that are developed by this process of venture membrane and sosification is this bone right here in the front you know you have a suture here and these are very important very important structures that during the baby whenever they're developing we'll talk about those in a second but here this bone in front of this coronal suture here is called your frontal bone so that's developed by the process of intra membranous ossification then the bones here on the side of the sagittal suture this is called your parietal bone okay you have two of these bad boys though right and then this one here in between this lambdoid suture is called your occipital bone now you guys might be like wait zach you said the occipital bone was developed from intra the endochondral ossification up here that's true but if you take again that cut here where you're kind of slicing through you're going to have a piece of that actual occipital bone that you're going to take from the calvaria but again you're also going to have the base of the occipital bone underneath where the occipital condyles come off as well so you're going to get occipital bone the top of it developed by intra membranous and the base of it developed by endochondral ossification okay now again i want you to remember these sutures because they help to separate things so this suture here is called your coronal suture okay this is called your coronal suture these are important uh uh clinically that we're not going to go into all of it but there is importances to this actual sutures if they don't actually completely uh if they close too early we call them craniosystosis types of conditions but this sushi here which separates the parietal bones is called your sagittal suture and then last but not least this suture here is called your lambdoid suture okay and these respectively kind of separate all these bones from one another one more thing is these little puffy things these little open areas of the skull that are very very important where the baby is developing these little areas where more than two bones kind of come together so you have the parietal bones in the frontal bone kind of coming together you make this little kind of opening here which kind of allows for the baby's skull to continue to like as the brain continues to grow during embryological development you have to have the skull kind of grow to accommodate that also when the baby's being born that skull needs to be able to kind of move and glide a little bit and so sometimes these fontanelles allow that to happen so here we have this fontanel which is where more than two bones are coming together in this case frontal and the parietals this is called your anterior fontanelle and these can also be monitors of intracranial pressure if there's high intracranial pressure what do you think that fontanel is going to do it's going to bulge out and if there's low endocrine pressure what do you think the fontanel is going to do bulge in right then you have the fontanel back here this one here we're going to swoop it around here in a second but this right here is where the occipital and the parietal bones meet what is this one this is called your posterior fontanelle now these eventually close this one closes first and this one closes a little bit later okay but again and knowing their importance is for allowing for the brain to grow we need to allow for the skull to continue to expand and also kind of that flexibility during the birthing process all right beautiful we talked about the neurocranium let's hit that viscera cranium all right ninja nurse so we just finished talking about the development of the base of the skull right the chondrocranium and then we talked about the top of the skull the cranial vault which was the membranous neural cranium right now what i want us to do is talk about the structures that are developing for the face which is your visceral cranium okay so now let's talk about the good old visceral cranium now the visceral cranium develops a little bit differently than what we talked about you would think oh it's going to develop from the mesoderm well it actually develops from some structures called the pharyngeal arches we'll go over these in more detail in the future but what i want you to think about here is we have a sagittal section of the embryo right and you can still see the ectoderm you can still see the mesoderm and then you can see the endoderm but you're seeing this in kind of like a different way a sagittal section here is showing you kind of from cranial to caudal fashion okay whereas the cross section you're kind of seeing that in a different view so what i want us to do is take a section about right here in the top of this tube here and what you're going to do is you're going to kind of cut this and zoom in on it and what you get is this very specialized structure we'll go into this in more detail but this is going to be called your pharyngeal apparatus and you see these like little kind of like vesiculations here how you have like this fasciculation here and then this one here this right here are called your pharyngeal arches okay so you have these pharyngeal arches the one that we care about for the development of the visceral cranium is your first pharyngeal arch okay so the first pharyngeal arch is going to be the structure that's going to develop into the viscerocranium there is a teensy bit of the second pharyngeal arch for one little bone and we'll talk about that one uh but other than that for the most part all the structures of the visceral cranium a very teensy bit of the second fringe arch but mainly the first pharyngeal arch is going to be the structure that develops into your visceral cranium all right and the same process happens here if you look at the pharyngeal apparatus here i kind of color coded it so you can see the outer part of the pharyngeal apparatus this blue color is ectoderm the big chunks here in the middle is your mesoderm and then this inner chunk here which is going to be what's coming called the primitive pharynx is going to be the endoderm the mesoderm chunk of this pharyngeal arch is going to be what really turns into the visceral cranium and it's the same process we'll talk about again that mesenchymal to cartilage to bone process in a second all right for the visceral cranium the main structures is the bones of the face and they develop in kind of like these process we have the first fringe arch it kind of gives us called a ventral and a dorsal component of it but what happens here is you're going to get some bones that are going to be made from this what are those bones this bone here that's made from the first pharyngeal arch is going to be called the mandible okay so you're going to form what's called the mandible the other one here is going to be this bad boy up here on the top and this is going to be called your maxilla then you have this bone up here your cheekbone what is that bone here called this bone here is called your zygomatic bones okay then you have another couple bones here left okay back here you have this bone portion here it's kind of coming up like this there's a little suture here we're not we can't really completely see it but it's called your squamous suture okay below that squamous suture is going to be a part of the temporal bone so what is this part of the temporal bone called this is called the squamous part of the temporal bone and on top of that there's also another little portion here you see this little hole here that's coming on that squamous part of the temporal bone this structure right here is actually called the external acoustic meatus these are all developed from the first pharyngeal arch now again going back to this what is the way that they're going through this process very very important all of this is happening through a very specific process you're taking these mesodermal cells they're differentiating what are they differentiating into straight into bones so if they're going from the mesodermal cells straight to bone tissue let's go ahead and recap you guys brains on this what is this called this is called intra membranous ossification beautiful now intra membranous ossification we already said what parts developed from the top of the skull and then including the facial bones there's only one other area the clavicles everything else is endochondral ossification all right beautiful there's a couple other components that i just want to mention they're developed from the first franchise let's come down here what are they all right so you have some bones that come from the actual first frangel arch and move their way down into the neck make a couple bones here in the neck right what are those bones and cartilage the first bone here is going to be what's called the hyoid bone so one of these bones here is called the hyoid bone the other that are not bones are these blue components here these blue components actually are going to be what's called what the laryngeal cartilage cartilages right and when we talk about these laryngeal cartilage so the laryngeal cartilage what are the two components of the laryngeal cartilage that we actually see here there's a bunch of we're not going to go through all but i'm going to i'm going to tell you there is the thyroid cartilage there's the cricoid cartilage there's the arytenoid cartilage right and then there's the cuny form cartilage but all of these are developed from the first pharyngeal arch so we got the hyoid bone we got the laryngocartilage guess what else little bones that are in your actual middle ear what are these two of them here are developed from the first fringe arch what is this one this one right here looks like a mallet right so we call this one malleus and this one here looks like kind of a little anvil we call this incus there's one other one and that's actually the one that's developed from the second pharyngeal arch okay i'm going to do this one in a different color so again i want you to remember that this is not from the first french arch this is actually from the second pharyngeal arch what is this one here called this is called stapes but again what do i want you to remember this is from the second arch okay very very important all right for embryological see now what's important also to mention here is that the mesodermal cells that actually convert into this bone particularly the bones go through a very interesting process you take the mesodermal cells what do they do they undergo differentiation process when they differentiate what they turn into they turn into cartilage then from the cartilage then what do they turn into some of it will stay as cartilage right like the laryngeal cartilage but the other components the hyoid bone the mouse the incus and the stapes will do what they'll convert into bone and when they convert into this bone tissue what is this process here called this is called endochondral ossification okay all right beautiful so what have we done so far we made the base of the skull we made the top of the skull we made the face and we made a couple other bones in the neck and in the ear now let's go on to talk about the trunk all right ninja nurse so we've talked about the skull let's go to the trunk let's start making our vertebrae let's start making the ribs let's start making the sternum so from this process we're going to have to again take a look here at our developing embryo when we take a look here at our developing embryo what do we have here again you got your neural tube you got your notochord you got your par axial mesoderm here on the sides you got your intermediate mesoderm and then you've got your lateral plate mesoderms right what i really want us to focus on is what part i wanted to take this neural tube out and yank this sucker out and then take the paraxial mesoderms and put it here on the side okay before we go through this kind of what's called re-segmentation process i want to talk about what happens to this par axial mesoderm all right so now before we start going through this kind of like re-segmentation process what i want us to do is again we're going to take the neural tube and on the sides you get your par axial mesoderm i just want you guys to understand what actually happens to this paraxial mesoderm a little bit so let's go ahead and take and kind of zoom in on pulling out that notochord and the actual par axial mesoderms on the side in a cross-sectional view so if we look at this what do you have here again you got your neural tube here right you got your nodochord right there in the center on the sides you have your paraxial mesoderm what happens is the paraxial mesoderm starts to develop these like little holes in it and what is that called so this is going to be your paraxon mesoderm and what happens is they start forming these little segments or chunks along the length of the notochord that are called somites but these so might start developing these little holes in them called somatoseals so this is a somite a chunk of paraxial mesoderm is called a somite but this right here is called a somato seal of the somite okay so you got your somatoseal what happens is this somatosteal continues to keep expanding and expanding expanding and as it does it cuts this actual somite into two chunks one is a dorsal chunk and one is a ventral chunk this dorsal chunk here is going to be what's called the dermatomyotome and this ventral trunk here is going to be what's called the sclerotome then what happens is the dermatomyotome even cuts in half again and forms into two separate chunks so now this becomes the dermatome on the back which is going to obviously make your dermis and subcutaneous tissue underneath that you're going to have muscle so this is going to be called the myotome later there is another one we'll talk about that in the muscular system called the senditome okay but then this one right here is going to be the scleratone oh man this stuff is so cool man isn't it crazy from ninja to nerd i want you guys to comment where you guys are at in this video alright make sure you do that all right but what i want you to remember here with the scleratome is the one that i really want you to focus on here with the development of the axial skeleton this is the one that actually is going to come around and make the bones the vertebrae the ribs all of those things that are coming off so the scleratome please don't forget that one so we took the somites we went through this process of explaining it what i need you to next understand is let's say here we have the somites okay we pulled the somites out but i want you to remember what part of the somite is actually going to make the vertebrae and the ribs it is the scleratone here we have the somites in chunks if we kind of cut them in half let's color code this the top part is going to be the rostral portion okay and then this brown part here is going to be kind of the caudal portion so you have the caudal portion here okay and then here you're going to have the rostral portion in blue so again rostral is blue the caudal is going to be brown okay what happens is is in this situation whenever your actual neural tube continues to develop you have to have the nerves that come off of it and move through the vertebrae right and right now the way this is there is no intersegmental portion for the actual spinal nerves to move out from the neural tube so what happens is a very special process that these somites go through which is called re-segmentation all this is is to allow for this inter kind of uh vertebral space for the actual nerves to run through how does that happen very interesting what happens is is this actual uh caudal portion will actually get fused with the rostral portion so each one of these portions are going to move up and fuse with the one above it okay so now what happens here let's look the brown part should be on top and then what should happen to those blue portions they should now be on the bottom because the blue is going to fuse with the brown or the caudal portion is going to fuse with the rostral portion what is this called resegmentation why is important to allow for the intervertebral spaces for the spinal nerves to run through boom diggity all right and again that'll be allowing for these spinal nerves once the actual nervous system develops for that to run through isn't that cool and then what happens so now imagine here's your somites they went through the resegmentation process where caudal fused with the rostral okay and in this situation what happens you get the re-segmentation then this sclerotome that component of the somite is going to start doing what forming bone tissue right via the process of endocontrossification around the neural tube and the notochord how does that process work look at this isn't this insane so then once you have that here all of this actual sclerotome is going to start surrounding the no the neural tube which will become the spinal cord in this case all right so now we went through the resegmentation process now again what are these actual sclerotherms going to start doing they're going to start moving around this actual neural tube and the nodochord and when they start doing that they're going to start forming the vertebral arches which are going to kind of wrap around this actual neural tube so now you're going to have a vertebral arch right here and then you're going to have a vertebral arch over here they're going to fuse and when they do that you're going to get this little point here at the end called your spinous process right and then what else is going to happen besides forming that they'll continue to form in the anterior portion here so when they form around the anterior portion what else are you going to get you're going to get the vertebral bodies and some intervertebral discs there as well then coming off of this portion you're going to have what's called your transverse processes right but then bone will continue to grow from that transverse process and a little bit of the body what is this going to be called these are going to become your ribs so from this sclerotome which is formed from the par axial mesoderm which gets undergoes this chunking process called forming somites re-segments then from that re-segmentation the sclerotome of those somites surround this portion and make the bone or the vertebrae and the ribs coming off of it isn't that cool so that's the that part there now let's make the sternum and connect the vertebrae and the ribs to it where does that come from all right so we formed our vertebral column right from the scleratome component of the somites we went through the process of re-segmentation and then we talked about how that completely sclerotine push into somite made the vertebral column ribs now let's go ahead and make the sternum this part's a little interesting so we have to kind of take a quick look back over here so remember we had this lateral plate mesoderm remember we had two components of it one here this component here i'm going to kind of asterisk that part that's the splanchnic layer of the lateral plate mesoderm and then this portion here was the somatic layer of the lateral plate mesoderm where do you see this kind of like ladder plate museum kind of coming you see it kind of like right here that is the anterior portion of the actual what that's the anterior portion of the embryo so if this is the anterior portion of the embryo guess what that ladder plate mesoderm is going to do this lateral plate mesoderm is actually going to do what the mesodermal cells will then convert into cartilage so here we're going to have our cartilage kind of like model here that we're going to go from now when we have that differentiation from the mesodermal cells to the cartilage model that was one step now that cartilage is then going to start converting into bone what does that process call mesodermal cells to the cartilage to the bone this is called endochondral ossification you're getting the point right that endochondral makes up most of the actual bone formation now this process where you make the bone we're going to have this cartilage model it's going to lead to bone that's going to fuse and form three components of the sternum what are the three components of this sternum this whole thing here is your sternum but it's made up of three points this part here is called the manubrium this is called the manubrium it's fused to the body via what's called the sternal angle or the angle of louis and then you have this zyfasternal joint here and that is going to be connecting the body to the xiphoid process so then you have your xiphoid process this is all going to make up your sternum which is going to be coming from the lateral plate mesoderm to the cartilage model to this bone then if we take the sternum this is in a three-dimensional space right this is formed from the lateral plate mesoderm imagine from the par axial mesoderm which part scleritome you made the vertebrae you made the ribs the ribs are starting to come around grow girl girl grow grow connect to what the sternum babushka all right so now we had the ribs formed from that actual par axial mesoderm the vertebral body and all the intervertebral discs connecting to the sternum we just made our what trunk let's move on now to the limbs all right so we formed so far the skull we've formed the trunk let's finish this up strong ninja nerds let's go into the limbs the limbs are going to develop from two components of the mesoderm so so far what we've seen is we've seen par axial mesoderm evolved a lot we've seen some neural crest cell and we saw a tnc bit of the lateral plate mesoderm well the lateral plate mesoderm is coming back again so what happens well in order for us to start forming limbs what happens is is we have to first know where do i want to put the limbs that's the first thing that i need to do where do the limbs need to go okay so i need to know the position of my upper limbs and the position of my lower limbs to grow from the embryo all right we're calling them limb buds so in other words i need particular genes to get activated in order for me to find the position to start initiating the formation of limb buds what are these genes it's very important that you know these genes these genes that'll lead to kind of the starting of the position so the position of the limb buds kind of getting this whole process initiated is going to be your hawx genes so you have different types of hox genes that are going to be activated okay other genes that will be activated in this process are going to be what's called tbx genes and the tbx genes will kind of determine a little bit particularly the formation of where the upper limb bud's going to come and the lower limb bud is going to come so the position will be kind of started and initiated by the hox genes but the tbx4 and tbx5 genes are really what's going to determine the position of the limbs which one's going to be upper which one's going to be lower when these genes are activated they then do something very interesting which is they help to lead to the actual development or differentiation into particular types of they lead to the production of particular growth factors that will be released in high concentrations and this is called fibroblast growth factor 10. so these genes will be activated for position this will be kind of activated for knowing which one's upper which one's lower and this one will be secreted for a particular reason which is allowing for the actual continued growth of the limb buds and we'll explain how so here we're going to have the upper limb buds and here we're going to have the lower limb buds we're going to abbreviate them for simplicity's sake so here's going to be our upper limb bud and here's going to be the lower limb buds now these are going to be the ectoderm so you obviously know this is our ectoderm then we have our mesoderm and then we have our endoderm right so the ectoderm is going to kind of grow off here these little limb buds that are going to come off now which part of the mesoderm do you see has quick easy access into the limb bud the ladder plate music which component of the ladder play music you guys better know it this is which one splenic this one is the somatic layer so what is going to happen is this somatic layer of the actual lateral plate mesoderm will start moving into these limb buds and when they start moving into the limb bud something interesting starts happening let's talk about that okay that fibroblast growth factor 10 what it does is it stimulates this little area here at the tip of the limb buds we're just zooming in i'm just i'll look at this limb butt here okay we're just going to zoom in on this one and we're going to only focus in on this limb bud when we look at this limb bud there's this little thickened area on the tip of that actual limb bud and this is the ectoderm what is this thickened area here called this is called the apical ectodermal ridge okay commonly abbreviated the aer what happens is the fibroblast growth factor type 10 is going to stimulate this apical ectodermal ridge what the apical ectodermal ridge will start doing is is it starts actually secreting other growth factors and when it starts secreting these growth factors it starts stimulating this lateral plate mesoderm that invaded into the limb bud to start proliferating what are these growth factors this one seed creates two types of growth factors one is called fibroblast growth factor type four and fibroblast growth factor type eight and these are going to start initiating tons and tons of proliferation of the lateral plate mesoderm now when it does that the portion of the lateral plate mesoderm that is closest to the apical ectodermal ridge will get hit with so much of these growth factors that all they do is proliferate they don't have time to differentiate that's very important so this area let's kind of imagine that i kind of do like this let's kind of say just this chunk here okay this chunk here of the lateral plate mesoderm that is closest to the apicolactodermal ridge this is going to be proliferating a ton so we call this the progress zone or the proliferating zone sometimes abbreviated as pz now as these cells these mesoderm cells start proliferating and proliferating and proliferating this allows for what happening the limb bud to continue to grow from proximal to distal so what is allowing for proximal to distal growth apical ectodermal ridge and these growth factors interacting with the progress zone i can't stress that enough that is for proximal to distal growth now as the limb bud continues to grow from these growth factors remember what i told you pretend here for a second i'm going to kind of erase this for a second this was just for a second that was that lateral plate mesoderm right and then this portion here was our progress zone this portion here was our apical ectodermal range releasing those growth factors we said the mesoderm closest to that proliferates but what about the mesoderm that's far away from the apoglectoma ridge what happens to that well growth factors are really saturated in this area but they're not really saturated much in this area so they don't have time to proliferate here whereas they're proliferating a ton here so if they don't proliferate guess what they do they differentiate and if these mesodermal cells differentiate what do you think they differentiate to cartilage then from cartilage to bone what is that called endochondral ossification so what are we going to make bone and this bone here that we would have just as a kind of an example here would be our humerus right if we're looking at the upper limb bud so that is this process now let's come down and talk about what happens next to the limb bud all right cool so so far what we've done is we've gone through this process of where we've done and made bone from the actual differentiating mesodermal cells and not the proliferating ones now another thing that starts to happen okay again let's kind of fast forward a little bit we have the humerus here was our progress zone what happens the limb bud continues to keep extending from width what direction proximal to distal so now here's our new progress zone as this limb bud continued to keep growing this was one part which was the humerus right you know what actually they call this embryologically they call this the stylopod because technically the limbs are developed in three components now this progress zone continued to keep growing so technically if you wanted to think about this this right here would have been that kind of ladder plate mesoderm that wasn't having a lot of proliferation so it did what differentiated what did it differentiate to cartilage then it differentiated from cartilage into bone what is that called endochondrification this portion here is called the zugopot even though technically we just call it the the forearm right now the next thing that happens is here's your progress zone here is the apicollectroderma ridge it's still thickened here we'll thicken it even more here for you this is still thickened but what happens is some of the tissue in the apical ectodermal ridge starts actually undergoing apoptosis so there's some little bit of apoptosis here in between the apical ecodermal ridge portions and this is due to high levels of bone morphogenic protein and retinoic acid these levels the change in these levels lead to apoptosis of some of the cells in this apicolectoderma ridge and it kind of starts doing what forming what looks like fingers right now there's still apical ectodermal ridge here so it's still releasing what fibroblast growth factors type four and eight so that's still telling the pro the actual progress zone to proliferate so where does that progress zone start proliferating into into these like little digits what looks like it right now as you again come down here to the next part here was the progress zone and kind of like the wrist and finger region what do we say as you get farther away from the apocalypto dermal ridge what starts happening to those mesodermal cells they differentiate into chondrocytes then from chondrocytes into bone tissue and now we're gonna have kind of the carpal bones then from there what else is gonna happen then this actual progress zone infiltrates into these like little digital components and that is going to start making your metacarpals and your phalanges that are going to extend into this now how this happens though how do you just prevent the fingers from continuing to grow well guess what happens to the apicollectoderma ridge the apical ectodermal rage in this next step here starts dying off it starts dying off and as the apical ectodermal ridge dies off what happens to the fibroblast growth factors they drop what happens to the progress zones they don't keep proliferating if they're not proliferating what are they doing differentiating and eventually this converts into bone and no more growth will be occurring here from proximal to distal origin now that covers the proximal to distal growth of the limb bud big things you need to remember apogeoderma ridge is driving the progress zone how is it doing it by these fibroblast growth factors now apoglectodermary starts breaking down you get the digits progress zone infiltrates it you get bones there this last portion here right we said stylopod zugopod technically this last portion here is called the autopod and again we just like to call it the wrist on the fingers right but that's kind of the embryological term for this kind of development now we talked about proximal to distal now what i want us to do is hit anterior to posterior development or a simple way of saying it how is our thumb look this way and look on this side and our pinky this way and on this side all right so we formed pretty much the limb bud right we went through that entire process from proximal to distal so we know how to actually extend the limb bud out now how do i make my hand look the way it does particularly from the thumb to the pinky how do i get this kind of configuration very interesting so i want you to imagine obviously this isn't the most perfect thing but i want you to imagine all these fingers and this diagram are exactly the same they look all alike we don't know which one's the thumb which one's the pinky right well we have to start developing that process so on the actual kind of like a dorsal portion here during embryological development this is kind of the posterior portion there's a little condensation of tissue here called the zone of polarizing activity we call this the zpa right but we'll write it out here the zone of polarizing activity this is what drives the anterior to posterior development of the hand in other words the thumb on one side pinky on the other side how does it do this well it starts releasing particular types of molecules that kind of kind of create a gradient throughout the actual hand region right particular types of molecules that create a gradient and those proteins or growth factors that are actually there depending upon that gradient creates the growth of this distinct differences in our actual fingers on the hand all right so what are the genes for the dorsal aspect of the hand that's going to be this wint 7a genes and these wind 7a's will actually induce the activation of what's called lmx1 and the lmx1 guess what it's going to do it's going to lead to stimulating the dorsal hand growth in a specific type of way what way can we distinguish the door socks by the hand from the ventral the nails right so it's going to kind of lead to the particular kind of growth of the nails and other aspects of how the dorsal aspect of the hand is grown the ventral right the ventral is by this process of engrailed one engrailed one genes when these are activated they are going to stimulate the ventral growth of the hand and what are one way that we can kind of distinguish that the ventral hand growth is going to be via what process this is going to be from the actual fingerprints now what is really important that i need you guys to know here is that the dorsal and ventral aspect of the hand this is primarily mediated by what tissue what do you notice here did you notice any mesoderm involved in this no this dorsal and ventral aspect of the hand is carried out by the dorsal and ventral ectoderm i need you to remember that so this is actually carried out by the ventral ectoderm and the dorsal ectoderm not the mesoderm all right engineer so let's finish up talking about intra-membrane estosification and endochondral we know what bones are developed from which ones right it's pretty straightforward endochondral is pretty much all the bones in the body the only ones for intramembranes are which ones do you guys remember the top of the skull and what else the facial bones and the clavicles that's it everything else is endochondral the last thing i want you guys to know though is how because this is important to think about yeah we know the process but how do these cells turn into these cells turn into these cells it's based upon the genes that they're expressing so whenever these uh particularly mesenchymal cells right so these mesenchymal cells whether this be from uh the ectoderm whether this be from mesoderm the par actually uh the soil particularly the paraxial mesoderm the neural crest cells whatever these mesenchymal cells have to activate particular genes to turn into bone cells what are these genes that they've seen most commonly involved in this the genes that you most likely see that are involved in this process are what's called the cbf a1 genes and the run x2 genes whenever these are activated they lead to particular proteins that give the phenotypic development of what types of cells osteoblasts okay and obviously osteoblasts have other phenotypic variants that allow for them not only to look different but to function differently produce different things like osteoid and different types of collagen so on and so forth same concept here so we obviously know that the cbfa1 genes are important for the development of and run x2 genes are important for the development of the bone cells but what about the conversion of mesenchymal cells to chondrocytes so going from mesenchymal to chondrocytes because we already talked about the osteoblasts we already know what genes are primarily involved in this process what about the chondrocytes there's particular genes here and the main gene that's involved in this is called the sox9 gene and the sox9 gene whenever this is activated leads to obviously the complete phenotypic development of chondrocytes with the ability to produce different types of proteins and molecules that distinguish them from other cells this is going to pretty much give you everything that you need to know for the development of the skeletal system all right ninja nerds so in this video today we talk about the development of the skeletal system i hope it made sense i hope you guys enjoyed it all right engineers as always until next [Music] time [Music] you