Transcribed by Erica Manion Craniofacial Biology Lecture 4 Prenatal Craniofacial Development I by Dr.

Wishe

3.24.14

[Slide 1] Facial Development I Dr. Wishe: Alright, well start in another minute. Welcome back. Hopefully everybody had a nice rest. Being prepared now for the next part of the course, and before the midterm you had three lectures in this course by Dr. Saint-Jeannet. General embryology. We are now going to use some of that information to discuss the formation of the head and the neck. And we have quite a few lectures on that. And then somewhere down the line, a little bit out of sequence, there will be a couple of lectures on post-natal development, which is your lead in to orthodontics. [Slide 2] - L FIG. 17.3 ARCH/LIMB DEVELOPMENT 12TH ED. Now he must have shown you some pictures that look like this. Initially the embryonic disk is a two layered structure. Your bilaminar germ disk consisting of the forerunner to ectoderm and the forerunner to endoderm. Epiblast and hypoblast. And then you get the formation of the third layer, which becomes the mesoderm. So initially we basically have a flat disk, just like Im illustrating with my arm. Then a processes takes place called bending or flexion. And essentially if you just look at what Im doing with my arm, thats flexion, actually thats longitudinal flexion. Theres also a transverse flexion. The embryo cant keep growing straight out, so it bends up in itself, and thats what youre basically seeing in these three pictures. A, B, and C, demonstrates the highest percentage of flexion. And because of the flexion, you get a space created right in here, shows it better right there (in image B, indicating the space between the lens placode and the heart bulge, anterior to the pharyngeal arches), thats the forerunner to the oral cavity. If you watch my hand itself, Im bending the hand, and the space in here is going to be the primitive oral cavity, or the stomodeum. The third diagram its hard to see the oral cavity, everything is jumbled up. The heart itself, this pericardial bulge, it looks like it develops outside the body. It really isnt, it is covered by skin and various other tissues, its just that the embryo has to grow a certain size so the heart can literally be sucked into the thoracic cavity. What we are concerned with is whats developing in this area (indicating pharyngeal arches of figure B). And these are your pharyngeal arches. Different species use these arches for different things, take something like a fish. Has got gill slits, so the branchial apparatus develops in the fish and certain amphibians for purposes of breathing. We have a completely different system which involves lungs, so we dont need this arch apparatus for lung breathing, for intake of air, getting rid of CO2. Going on in development, youll see more and more of these arches form. Essentially they begin to form somewhere between the fourth and fifth week of development, and the arches give a characteristic external appearance in this region which is going to be the head and neck. What we also he here is a little region, well get to that much later on, otic placode. Placode means thickening, and the fact that this is otic relates to the ear. In the same fashion, in 1

this part of the embryo you get another thickening, your lens placode. So thats involved in heart development. And finally, the last picture shows limbs developing. We call them limb buds. And the hind limb buds, in fact the whole hind or caudal part of the embryo tends to develop much slower then the cephalic part. [Slide 3] - L FIG. 17.5 FACE/ARCH DEVELOPMENT 12TH ED. Heres a head on view of the embryo. The others were side views. And what we are essentially seeing, particularly if you look at diagram B, happen to be the first and second pharyngeal arches. I use the term branchial and pharyngeal synonymously. But when you are dealing with animals with gills they tend to use the term branchial. And for us, or any lung breathing animal, we tend to use the term pharyngeal, but I use them interchangeably. And as you look, this is somewhere between fourth and fifth week of development. You can identify several different prominences. From the first branchial arch, youre going to get a splitting up and the formation of a maxillary prominence. We can use the word process as well. And then theres a mandibular process or prominence thats right over here. And the terminoligy uses the term, thats the mandibular arch. Then we have a big bulge on the top known as the frontonasal prominence. And in between, in this particular area, theres an opening. And thats the primitive oral cavity, or stomodeum if you like. Initially it starts of small, and it gets larger as you can see in diagram B. As you look at the frontonasal prominence. You can see these two areas. Theres this area, and this area, where youre having an ectodermal thickening. We use the term placode. And this is the nasal placode. Obviously its going to give rise to the various parts of the nose. Heres a pic of a mouse embryo showing you the frontonasal prom, hard to see but up in here is that nasal placode. Heres your maxillary prominence, and theres the mandibular prominence. And the second arch is coming in a little bit lower, and thats the hyoid arch. We are going to go over all of this material [Slide 4] - L FIG. 17.6 PHARYNGEAL ARCHES 12TH ED. The top most pic is showing you the caudal end of the embryo and the dotted line represents where the embryo was cut. So it was cut in a fashion like this, so as a result when you look at the cut surface, these are the various structures that you will see. In the head area youll get the neural tube developing, and thats what this represents. In the tail area which were not really concerned with, if you continue the embryonic diagram further down youll find the spinal cord. So in essence youve got this kind of cut going through here.

These are the arches and they number six, except in humans we basically have four. In oxygen CO2 exchange methods, six are required to take care of your special needs of your fish and other creatures that have a gill system. You can think of these arches as bricks, and youre putting one brick on top of another. As you look at the outside you see a blue covering. What does blue represent? Ectoderm. Wherever you see blue, that particular area came from ectoderm. Then as you look on the inside, you see yellow. What does yellow represent? Endoderm. Then in between we should have some mesoderm. But when you look at different parts of the body, there are two sources of mesoderm. Below the neck you get mesoderm developing directly, but when you look in the head and neck you find theres another basic tissue, which Im sure Dr. Saint-Jeannet spoke about, neural crest. And neural crest is derived from the ectoderm itself. And this neural crest in the face and neck will give rise to your mesenchyme, your basic embryonic tissue. Whereas in the rest of body, mesoderm gives rise to mesenchyme. So there are two different sources which lead to the formation of your mesenchyme. Here you are looking at the inside of the embryo, the pharyngeal area, etc. at this point in time youll see these indentations from the outside pushing into the arch. Those are called pharyngeal clefts or grooves. You also see from the inside pushing out, or pushing into the arch, regions called pharyngeal pouches. Each one of these areas gives rise to something different. As we look at each of the arches youll see different colored circles. Red represents the vascularity, yellow is your nerve, and the white happens to be your cartilage. Actually it looks white to me anyway. Each arch has its own nerve supply. Each arch has its own aortic arch, alias blood vessels. Each arch has a forerunner to the cartilage thats present in each arch. [Slide 5] L FIG. 17.7 NERVES 12TH ED. This particular picture shows you the nerve distribution in the entire arch region. CN V, trigeminal, is associated with arch one and it has three branches. Opthalmic branch, maxillary, and mandibular branch. Arch number two is associated with the facial nerve, CN VII. Arch three is associated with the 9th CN, glossopharyngeal nerve. And arch 4 and arch 6 are associated with the 10th CN, your vagus. So each arch has its own nerve supply. [Slide 6] L FIG. 17.8 CARTILAGE DEVELOPMENT 12TH ED. This is showing us the presence of cartilage developing. In the first arch you get a piece of cartilage right here known as Meckels cartilage. Most of mandible forms intramembranously, so dont think for a moment because we have such a large piece of cartilage, its going to give rise to the mandible. It doesnt. What Meckels cartilage does give rise to is the area where you have the mandibular symphysis, And then you turn to the TMJ, the temporomandibular joint, and the malleus, and incus is derived from Meckels cartilage. Then we look at the second arch. The cartilage there has a specific name, its called Reicherts cartilage, and Reicherts cartilage will give to the third middle ear bone, the stapes. Cartilages in arches three and four dont necessarily have names. [Slide 7] L FIG. 17.9 CARTILAGE DEVELOPMENT 12TH ED.

And here we see more detail in terms of cartilage development. And all this which is Meckles cartilage will disappear except in this area. And then you get your Malleus, and the Incus. We turn our attention to the 2nd arch, and theres the stapes forming from Reicherts cartilage. It also gives rise to the styloid process and the styloid ligament, and it plays a role in the formation of the hyoid bone. In essence its forming the lesser horn of the hyoid bone and the top of the body of the hyoid bone. In the 3rd arch, the cartilage present there essentially forms the rest of the hyoid bone. Your greater horn and most of the body. Then we go to the 4th arch, and that gives rise to thyroid cartilage. 5th arch doesnt exist with us. 6th arch, there are some remnant components and the cartilage present in the 6th arch also contribute a little bit to the thyroid cartilage as well as forming various cartilaginous structures right underneath the thyroid cartilage like the cricoid. And as we further go down the trachea we get these cartilaginous rings. [Slide 8] L FIG. 17.4 BLOOD VESSELS 12TH ED. This shows you the development of the blood vessels that takes place in all the arches. Each arch, and if we figure six arches, even though we dont have six, each arch will have its own blood vessel. So heres aortic arch vessel 1, 2, 3, 4, and 6. The Aortic arch vessel essentially disappears. And maybe youll get it giving rise to part of the maxillary artery. Aortic arch vessel #2 also disappears but plays a role in the formation of some small arteries like the hyoid artery Its not until we get to the 3rd aortic arch vessel that we get the formation of a major component. The common carotid arteries which gives rise to the internal and external carotid arteries. The internal carotid, as you remember from anatomy, went up to the brain, and the external carotids supply blood from the neck going up towards the face. Then the 4th aortic arch forms your actual aortic arch, in other words, this part. And then the 6th aortic arch will give rise to the pulmonary trunk and pulmonary vessels. Did dr. Saint Jeannet go over fetal modifications and stuff in his lectures? You know like ductus arteriosis and all that? He did? Ok. [Slide 9] L FIG. 13.37 AORTIC ARCHES 12TH ED. Now the next picture youre not supposed to get spaced out of. This just shows you the formation of the various major vessels. So in reality when we start off, there are two dorsal aorta. And these are the various aortic arch vessels, and these are showing you 1 through 6 as a general development. 1 and 2 disappear, thats why you have the dotted lines here. And the third one will give rise to your common carotid which then splits into the external and internal carotids. The fourth one, heres your arch of the aorta, and the 6th one plays a role in the formation of this pulmonary region. And the ductus arteriosis, just to refresh your memory, is a shunt that bypasses the lungs. Cause while youre inside mom, youre never really breathing. Your 4

getting oxygen from here, and shes taking away the CO2 from you. So you dont need a functional respiratory system at that point. Eventually when you are born, this ductus arteriosis should seal up, forming this ligamentum arteriosum. And there are other embryonic shortcuts like the foramen ovale, between the right and left auricles or atria. Again designed to bypass the lungs. Some blood has to go to the lungs to keep the individual alive and keep the lungs in functional condition. [Slide 10] L FIG. 15.6 PHARYNGEAL ARCHES OLDER ED. Now we go back and we see four arches here. Ectoderm covering, endoderm lining. And you see the aortic vessel component, the nerve component, and the cartilage component. According to this diagram, this looks orange, and thats what they made as the cartilage component, where I guess this little yellow dot represents the nerve. And this is just a section through again a mouse embryo showing you the situation of the arch. And here you have a complete arch (Image C). Thats ectoderm, endoderm, and the tissue in between is really mesenchyme which has been derived from neural crest tissue. [Slide 11] L FIG. 17.10 PHARYNGEAL POUCH DEVELOPMENT 12TH ED. So. Arch number I will give rise to your maxillary and mandibular processes. And in the mandibular process we find Meckles cartilage. So this being arch I (back to slide 10), this little orange thing gives rise to Meckles cartilage. And the maxillary process will form the pre maxilla, the maxilla, zygomatic bone, and part of the temporal bone. Keep in mind all the bone development in the head for the most part is via intramembranous bone formation. But the base of the skull, which well talk about a couple of sessions down, starts off as hyaline cart. So the base of the skull will form via endochondral bone formation. Everything else in the head is intramembranous bone formation. Mandibular process forms the mandible. And most of mandible is formed from intramembranous bone formation. Goes from mesenchyme to osteoprogenitor cells and eventually you get bone tissue. But the endochondral bone formation at the base of the skull, you apparently dont have much of a vascularity so therefore you get cartilage forming which has a very low O2 tension, where bone has a very high O2 tension. Eventually when the vascularity enters the area the cartilage will degenerate and be replaced by actual bone tissue. (Back to slide 11) These two pictures illustrate for you whats happening to these pharyngeal arches. As you look at this picture (back to slide 10) you see these indentations which I previously mentioned as being pharyngeal clefts or grooves. From the pharynx pushing into the arch, youll find these indentations which are your pharyngeal grooves. This picture (Slide 11) shows you whats happening to them. It turns out that the mesenchyme from arch 2 continues to go through mitosis grows down and incorporates all the clefts. So by the time youre through, you only have one pharyngeal cleft. And all the others have disappeared except for this area, which is the cervical sinus. It can stay there, it can become a cyst, or you can have other problems, which well go over.

So 1st pharyngeal cleft gives rise to the external auditory meatus. And while Im at it, lets look at the first groove. Thats going to forms prim tympanic cavity middle ear cavity, as well as your auditory and eustacian tube. And where the ectoderm and endoderm come together, youll get a very thin sliver of mesoderm forming, so you three basic tissues making up your ear drum or tympanic membrane. And if you take a look at this area What Ive just drawn in represents your ear which develops from the mandibular process and the hyoid process of the second pharyngeal arch. Auditory tube becomes continuous with oral cavity. Therefore, some of us when we get sick, have a sore throat, the germs can spread into the auditory tube into the middle ear cavity and you end up with ear infection. When youre in an airplane, your ears clog up sometimes. So the pressure builds up in this tube and middle ear cavity. By swallowing, youre sucking out the pressure, reducing the pressure, so your ear doesnt hurt you. So that takes care of the 1st pharyngeal cleft and 1st pharyngeal pouch. Remember there are no other clefts. The 2nd pharyngeal pouch gives rise to your palatine tonsil. Then we go to the 3rd pouch and youll see two different colors. Yellow and red. Red-brown. Yellow part is the dorsal part of the pouch. Gives rise to inferior parathyroid gland. The ventral portion gives rise to the thymus. We go to the 4th pouch, it also has two components. The yellow and a blue. The yellow part will form the superior parathyroid gland. If you are fully awake and understand what I said, you should have a question in your mind. How can this be inferior, and that superior. Well theres movement that occurs, which well see in the next picture. And finally this little blue thing here gives rise to the ultimobranchial body, which gives rise to your Parafollicular c cells. Dont forget the parathyroid and the ultimobranchial body play roles in calcium metabolism, controlling mineralization. [Slide 12] L FIG. 17.11 THYMUS, PARATHYROID AND ULTIMOBRANCHIAL BODY 12TH ED. 1st pouch, 2nd pouch, and now what happens in the 3rd pouch is the thymus gland detaches from the wall and takes a trip in a more inferior direction. At the same time its pulling with it the inferior thyroid gland. And so along the pathway the two hug and kiss and say goodbye to each other. The thymus continues to move inferiorly and eventually comes to lie on top of the heart around where the right atrium is. This component which is the inferior parathyroid gland now moves where the thyroid gland is, the inferior portion. Coming of the fourth pouch, was the part that gives rise to the superior portion. It moves and becomes situated on the superior part of the thyroid gland. So that accounts for the difference in the terminology. Where the parathyroid components start and where they end is two different stories. And finally the ultimobranchial body also moves and situates itself in the thyroid gland, giving rise to your parafollicular c cells. [Slide 13] L FIG. 17.14 CYSTS/FISTULAS 12TH ED. To study this you really have to look at the pictures. Its not as complicated as it seems. The picture on the left. We have arch 1, arch 2. This is remnant of clefts two, three, four, and that was a sinus before. This sinus can stay as a sinus or develop into a cyst. A lateral cervical cyst. It could stay that way, not bother anybody, could become infected, then you have a problem. And sometimes a cyst opens up to the outside word through this little tube 6

structure here, and thats referred to as an external branchial fistula. Diagram B shows you spots where you could get lateral cervical cysts and/or fistulas. And they lie ventral to the sternocleidomastoid muscle. So theyre all lined up along that muscle. And finally diagram C shows you lateral cervical cyst with a fistula opening up into the 2nd branchial pouch. Again, we have air and food particles passing by this area and that could lead to infection of the cyst. But there is still one more scenario, and Im just going to draw this line, where you have an external fistula, cyst, internal fistula. Its a long, continuous tube. You could technically take a pipe cleaner, which is flexible, stick it into the external fistula, pass it through the cyst, and finally through this internal branchial fistula and pull it out through the pharynx. So this is a nice area for bacteria and debris to accumulate. [Slide 14] L FIG. 17.15 LATERAL CERVICAL CYST 12TH ED. And this is a picture of child with bulge right over here. Thats your lateral cervical cyst, and the sternocleidomastoid muscle would be located right there. [Slide 15] L FIG. 17.2 NEURAL CREST MIGRATION 12TH ED. During the formation of the embryo you get a lot of movement of cells. What this is essentially showing you is that neural crest cells, which are deposited on each side of the developing neural tube, will spread around that neural tube and flow into your various arches and into the head region. So this is just illustrating the migration of that. [Slide 16] L FIG. 16.16 FACIAL DEFECTS 11TH ED. Before we get into the pictures I now have, lets finish up the discussion about the individual arches. In terms of your musculature, the 1st arch will give rise to muscles of mastication, part or the temporal, anterior belly of the digastric, mylohyoid, and the tensor muscles, tympani and palatini. And again, just to refresh the memory, this arch is supplied by CN V. The 2nd arch will give rise to muscles of facial expression. And so the muscles of facial expression are starting to form in neck area and then they grow up over the face. Well see that when we do skeletal development. In addition it forms the posterior belly of digastric, stylohyoid, etc. The 3rd arch will give rise to your glossopharyngeal nerve, thats number nine, and the stylopharygeous muscle. And those are essentially your pharyngeal constrictors. Arch 4 doesnt necessarily give rise to much musculature. But around the thyroid cartilage youll find a whole bunch of little muscles.. Like the cricothyroid. And then arches 4 and 6 supplied by the vagus nerve. In arch 4 the vagus nerve gives rise to the superior laryngeal branch of the vagus, and in arch 6 the vagus nerve gives rise to your recurrent laryngeal branch of the vagus. And then youll get some laryngeal muscles developing also in arch 6. What we see here happens to be further misdevelopment, underdevelopment, whatever you want to call it. Picture a shows you someone with Treacher Collins Syndrome... Which I dont want to say is one of the more popular defects, but you tend to find people with this defect more 7

than the others. And all these arches involve mesenchyme movement. Neural crest mesenchyme migration. If migration of the cells doesnt proceed like it normally should, then youre going to get certain defects. During this developmental period, 4th 5th week, youre setting up potential forerunner for defects. You have to realize embryonic cells are sensitive. They will react to anything. So Treacher Collins Syndrome is actually involving arch 1,the mandibular prominence, and arch 2, the hyoid. And as a result of a dominant autosomal gene, something has gone wrong with genes and therefore you get abnormal development. And if you look at this picture, look at the external ear, you get malformed ears. Hard to see, but the palpebral fissures the opening between the eyelids, slants downward. This is where the maxilla ends, and thats where the mandible ends. So the two jaws and the teeth that develop will be out of occlusion. So heres a situation where you can use distraction osteogenesis to lengthen the mandible. I talked about that in Bone. Where you put a certain device on the mandible, it gets screwed into the bone, you fracture the bone, it begins to heal, you pull apart the bone, it heals. And you repeat that procedure until the mandible is in the right occlusal pathway. And youre trying to bring the mandible as close as possible to the end of the maxillary jaw. So youre going to have mandibular hypoplasia, under development of the mandible, down slanting of the palpebral fissures, malformed ears, and other things that could possibly happen. Picture B at quick glance looks normal. But there may be something thats not formed properly in terms of the ear. And again notice where the mandible ends and where the maxilla ends. So once again having under development of mandible. And once the mandible is underdeveloped, youre going to get some problems with the maxilla in both of these cases. Side effects and defects of branchial arch 1. And this condition is called Robin sequence. Now in terms of underdevelopment, some individuals as they grow, the mandible will further develop and the occlusion is not bad. You can fix both of these conditions up. Because the mandible underdeveloped, the tongue is pushed back more posteriorly. And depending on how far posteriorly the tongue is pushed, it might literally cover or block the entrance to the respiratory system, and that will give you problems with breathing. The word by the way, micronathia means underdevelopment of the jaw and is generally associated with the mandible, but you might have some conditions where things are reversed and you get underdevelopment of the maxilla. Most of these are low % occurrences, but they still do happen. This can happen because of something going wrong with chromosomes, genetics-wise, or teratogens. Youll have a lecture on teratology. A teratogen is something thats introduced to the body from the outside. Lets say mom likes to drink, and mom likes to smoke. You dont want to do that when youre pregnant because alcohol and nicotine could seriously effect development of the child and give you certain defects. Now I call this a syndrome, and not a sequence. The difference between the use of those two terms, which well get into momentarily is that a syndrome is caused by a series of events all happening together. A sequence is like you went bowling. You throw the ball down the bowling alley. It hits pin one, which hits 2 and 3, then 4 5 and 6 fall, so one line of pins fall at a time. So hit pin 1, now effects pins 2 and 3. sequential type of scenario. That s the only difference between the two. Picture C, and this might have been mentioned in organ systems, is the DiGeorge sequence. It might have been mentioned by Dr. Saint-Jeannet. If you look at this individual, doesnt look particularly bad, he might have some defects of the ears, notice the mouth it 8

seems to go up like a little pyramid shape. The eyes are too close together. But more importantly, is that this sequence develops from the derivatives of pouch number 3. So your parathyroid is going to be a problem. Could be missing, could be too small. And there fore you have a condition that develops, hypoparathyroidism. This has an effect on bone development. Remember the parathyroid gland released a hormone PTH, which stimulated osteoblasts which now would activate osteoclasts. If you go back to your schemes I gave you for bone, we are talking about RANKL/RANK scenario. More importantly, theres a problem with the thymus gland. Youre immunocompromised, and someone who has a defective or missing thymus gland has a very poor prognosis. And they havent made a movie about this in a long time, but they used to have a movie, boy in a bubble or girl in a bubble who had to live in a certain type of environment, germ free. When the individual went out, he or she would put on an astronaut suit, so they dont have to breath the air and get all the germs, because their immune system is shot. And again, all these conditions result from improper neural crest migration. Finally the last picture, you immediately see this area. This is called Hemifacial Microsomia. Its known by other names but this is the simplest name to call it. Again, it involves the formation of your maxillary, your temporal, and your zygomatic bones. You generally get malformation of the ear as well as with the eyes. And this might have been mentioned by Dr. Terracio, when he lectured on the heart concerning the Tetraology of Fallot. So this type of individual will have that as a defect. Why dont we take a ten minute break at this point. I believe its this Wednesday youll have a CCP on embryology. Hes never on time in terms of posting things. Theres nothing I can do about it. Im glad he comes in to do the CCP. But once we get through with facial defects, well enlarge on it.