Early embryological development What happens?!

Fertilization leads to the formation of zygote which is structure that forms from diffusion between the ovum and the sperm, which both have haploid number of chromosomes equal 23, and when both fuse together they form the zygote which is composed of 46 chromosome which is the number of chromosomes that we have in our body, following thatwe will have one complete cell(zygote) with full number of chromosomes, this happens at the distal part of the oval duct( 2shar 3la el: ovary duct, uterus, fallopian canal) once the sperm get inside the egg they form the zygote and the zygote start to travel , the unfertilized egg surrounded by a huge number of sperms, just one sperm can get inside the egg to fertilize it, and once it is fertilized it will develop impermeable membrane so other sperms can't get inside, the zygote travel through the oval duct and start to divide into 2 cells, then 4,then 8 and so on and finally 12-16 cells, the cell is called blastomere, this sort of division is mitotic division, which lead to the formation of same number of chromosomes, so we have tow cells stage which is called blastomere then we have four cells stage which is called blastomere too, after that we have 12-16 cells stage which called morula which is about 0.1-0.2 mm these morula start to develop a cavity inside it called blastocoel, and once the blastocoel is formed, the structure is ready to be implanted in the wall of the uterus, so it's called now "blastocyst";{ blastocyst = morula+blastocoele}. at this stage it's 100-150 cells but it still the same size, we have the blactocoel which is the cavity inside it and we have a tough membrane surround it called Zona pellucida , and at this stage because of the cyst we can identify tow groups of cell: 1.the inner cell mass will develop the embryo 2. The outer cell mass will be important in the attachment of the embryo into the uterus, then it will be implanted. (Pictures in slides 3-4 will really help u) Now the doctor goes back to the first slide, the Intra-uterine stage, as we know the intra uterine stages run on 9 months. We can divide this total period into three stages: 1. The first stage is called "Pre-embryonic" it is from fertilization until 2 weeks of age this involve Fertilization, Implantation and the bilaminar embryonic disk. 2. From week 2-8 this called the embryonic stage. 3.After 8 weeks until birth we can call it fetus(the doctor repeat several time that from 2-8 weeks we call it "embryo" and after that "fetus" and these terms are different), In the embryonic stage different types of tissues are developed but in the fetus stage there is an increasing in body weight and size, (y3ne ttkwan bl-embryonic stage otanmo fe el-fetal stage) that's why during the embryonic stage we don't need any environmental effects to cause any problem to the embryo ,for this reason usually the pregnant ladies should be very careful in this period about there babies(shouldn't exposed to radiations or taking specific type of drugs) in the first 3 months(embryonic stage),cause embryo is developing and structures is forming that's whay any environmental effect can cause problem, and just after the embryo is transformed into a fetus stage it just will under go increase in body weight and size ,so the environmental facts will have less effects on the fetus after the embryonic stage (doctor said you have to know this information for the exam).

Now the inner cell mass is just without any specification, later on the inner cell mass become tow layers and that's why we call it Bilaminar Embryo (y3ne el inner cell mass ele kant 3shwa2yeh etrtbt wsart bilayer), so we have two layers: 1. The epiblast 2.The hypoblast. The epiblast (epi=above) this will become the future ectoderm and the hypoblast will become the future endoderm so this means; at first we have the development of ectoderm and endoderm but later on we will have the development of mesoderm, (exam question; one of the following germ layer comes later on the answer is mesoderm) all of these changes happened and the embryo still the same size as the zygote (and this all what we have to know from the fourth slide). We have the Exocoelomic membrane which is continues with the endoderm, we have to know that once the structure (embryo) is implanted in the uterus it developed its own circulation (the blood vessels in order to attach the fetus with his mother), at this period we can call the structure embryo (all what we talk about before was pre-embryo) to understand the picture in the slide the doctor explain. That it will make a cut through the Amniotic cavity, and then I will view the top surface of the ectoderm, now at the beginning of the third week we have the Prochordal (cephalic) plate which is slight thickenings in the endoderm and this results in thickening in the ectoderm and this indicate the future head end of fetus and later on, this Prochordal plate become Buccopharyngeal membrane;which is the membrane that separate between the mouth and the pharynx, and it's Located exactly at the end of the mouth and the beginning of the pharynx. We have also the Caudal end (cloacal membrane) near the bottom or the tail of the embryo, at this stag we can see the development mesoderm which will start to appear at 17 day, mesoderm rounding up toward caudal midline spreading and rounding between ectoderm and endoderm and that will cause to the primitive streak to form. Most important to know: ectoderm and endoderm form first and then mesoderm which is form from ectoderm. Ectoderm cells start to grow in size and go down, between it and the endoderm the formation of mesoderm will occurs. By this the embryo consist from 3 main germ layers .and later on something called the Notochord process witch is a tube that start from primitive knot, from primitive knot a tube forms and go to the cephalic area between the ectoderm and endoderm that called "primitive knot", Again the mesoderm layer formed by going the cells into the midline but not in all area just in the coudal half of the disk then collided with each other and reflected down between the ectoderm and endoderm and this make the groove "primitive streak" that have in it's end the primitive node.

From primitive node a structure form and goes all the way down between the ectoderm and endoderm and it goes to the cephalic end to reach the prochordal end and this called the Notochord, the notochord is a progenitor of the back bone and vertebral column, by this mesoderm is located between ectoderm and endoderm and separate them from each other in all regions except.., (exam question: the third layer which is the mesoderm separate ectoderm from endoderm in all regions except? *prochordal plate, *notochorod itself and in the *cloacal membrane)in these three areas we don't see mesoderm.

The table in slide number 8, we have to memorize it by heart and to know the structures given from each layer, for example: Skin and appendages and all epithelia in the body is given by ectoderm and this including the oral mucosa, nasal mucosa, anal mucosa, sweat glands, hair follicles, Linings of nose and sinuses and most importantly is enamel, this information is important because we have a disease called ectodermal dyplasia, in this disease children have problems in structures that develop from ectoderm, like scanty hair follicles and missing teeth because they have problem in a formation of enamel also they have high temperature because they dont have enough sweat glands to reduce heat in the body. Another structures form from ectoderm like nervous system, pituitary and mammary glands and the lens of the eye. Regarding the endoderm it gives the lingual tonsils, the lining of the lung and the digestive system except the pharynx and larynx (u3ny starting from esophagus) and the lining of the excretory system. Now regarding the mesoderm, mesoderm gives bones and muscles and all connective tissue In the body also it's very important that it gives all the dental tissues except enamel this include dentin, dental pulp and all supporting structures (the gingival too but not the epithelium of the gingival cause the lining considered as ectoderm).Also lymphatic tissue and spleen, blood cells, heart and lungs, reproductive system and excretory system. Now we will move to the development of mesoderm, mesoderm develops into three different areas, notice that ectoderm and endoderm remain thin but we have thickening in the middle layer which is mesoderm, we have an area located in a notochord which is adjacent to the access we call it paraxial mesoderm, so paraxial mesoderm is the swellings of the mesoderm just next to the midline, then we are now in the intermediate mesoderm and the lateral plate mesoderm, now the most important to know is the paraxial mesoderm; it forms swellings or cuboidal masses that located in. Pairs on each side of notochord that called" somites", and they give the appearance to what we called chewed material, somites is 42 45 pairs by the end of 5th week. Intermediate mesoderm gives the: 1. Urinary system. 2. Adrenal cortex. 3. Much of reproductive system.

The doctor said that in the exam he will not ask as about the intermediate mesoderm and lateral mesoderm. Now each somaite is divided into three regions: 1. Dermatome,2. Myotome, 3.Sclerotom. Notice that the area in black is the dermatome and it's responsible to give the dermis of the skin and not the epidermis which is given by the ectoderm (dermis is the layer that located just below the epidermis), in the oral cavity we have the epithelium (top layer) that given by the ectoderm, and the connective tissue below the epithelium called lamina propria of oral mucosa is given by dermatome. Also we have Myotome which gives: 1. Vertebral musculature. 2. Intercostal musculature. 3. Some limb musculature. And we have the Sclerotome which gives the vertebrae, ribs and sternum.

The head somite These somites that exist in the head region are called prootic somite and metotic somite, they differ in that the prootic somite gives the muscle of the eyes and the myotome of the metotic somite give the tongue muscles ( myotome of 3rd 6th metotic somites ) . Q: The muscles of the tongue are from which of the following? A: The metotic somites; which are among the head somites. The eye muscles: 1. Superior rectus 2. Inferior rectus 3. Medial rectus 4. Lateral rectus 5. Superior oblique 6. Inferior oblique These muscles are supplied by different nerves but they are all from prootic somite

The folding of the embryo:

just behind to the prochordal plate we have the development of the brain develops as what we called the neural plate, imagine that the mouth when develops early is present more cephalic than the brain, in other words before the folding of the embryo the prochordal plate which gives rise to the mouth is more cephalic than the tissues that give the brain (VERY IMPORTANT NOTE).

So this is the oropharangeal membrane and just behind it we have the development of the brain and whats happened anterior to it, we have the development of the heart (the primitive heart) and have septum transversum that will develop the liver. So before the folding of the embryo the cephalic tissue is that which gives the liver and then the tissue that give the heart , the tissue that give the mouth and tissue that give the brain logically the most cephalic now is the brain the mouth the heart and finally the liver . So this means that we should have some form of reorientation and this is caused by the folding of the embryo.

So we will talk now about folding, at first the structure that develop the liver which is the septum transversum is located most cephalic behind it the tissue that develop the heart and then the oropharengeal membrane then the brain but because the folding of the embryo this folding of the embryo caused partly by the fast growing of the brain tissue which exceeds the other tissues. So the fast growth of the brain leads to adjusting the orientation of these tissue according to the anatomical locations, but early in embryogenesis the order of these tissue are really reversed. Now so far we have discussed new somites we said these are from mesoderm particularly from the paraxial mesoderm and we said these actually give some marks on the ectoderm so thats why the embryo appears like a chewed material and also we said that each somite is divided into three parts ( *sclerotome,*myotome,*dermatome) , please remember that the metotic and prootic myotome of the head or the cephalic somite are responsible of the formation of the eye muscles and the tongue muscles. Also then we talked about the folding of the embryo which is important and the folding actually orientates the structures according to the anatomical position, we know that they must be cephalic are the brain then the mouth, the heart and liver. But the order of these tissue before folding is reversed , and this folding caused by the rapid development of the brain, because its very fast it overlap the other tissues , so thats why they appear to be below it. The formation and the rapid development of the brain: Neurulation which is the Formation of Central Nerves system, at first the first signal of formation of the CNS is the Neural plate thickened mass forms in the overlying ectoderm and it is located just codaul to the prochordal plate. It starts as a plate then a groove forms in the midline and then this plate becomes a groove that is why it starts as a plate, the groove is deepened farther until it becomes neural tube until the whole neural tissue is separate from the ectoderm and becomes in the mesoderm And becomes the neural tube The CNS starts as a plate then the plate is deepened to have a groove "neural groove" and at the end it becomes tube. As the groove becomes tube we have some tissues located at the periphery of the neural plate, we call them the neural crest (VERY IMPORTANT), the neural crest originally belong to the ectoderm as the neural plate. Once the groove is separated from the ectoderm to become the tube also these tissues become separated from the ectoderm and now we call them neural crest cells these migrates and spread within the head region and these cells are responsible for the formation of dentin and dental pulp and cementum. Neural crest pinched off the neural groove to be separate and then these cell spread out through the mesoderm of the head

Because these cells are now located after migration they become located in the mesoderm but they are originally from ectoderm that is why we call them Ectomesenchymal tissue; it means that it is from ectoderm but now it is at the mesoderm So the neural crest is located at the junction of nural plate and ectoderm of the head region. The neural crest cells are called Ectomesenchymal tissue in head region these forms the Dermis of head region which is the connective tissue under the epidermis and also the lamina propria under the epithelium and also they form all dental tissue except enamel . As we mentioned before that all dental tissue except enamel are from mesoderm but to be more specific they are not originally from mesoderm, although they are within the mesoderm but they are from ectoderm and that is why we call them Ectomesenchymal tissue. They are responsible for the formation of brachial arches which are a number of arches develop in the neck region of the embryo. Also they give:- (VERY IMPORTANT) * Pigment cells- Melanocytes. *Skeleton- Part of musculature. *Meninges *Spinal & cranial nerve ganglia. *Sympathetic & parasympathetic systems. *Adrenal medulla. *Schwann cells. Development of epithelial structures The Epidermis is from surface ectodermal cells. The Dermis is from underlying mesoderm of somites, but the dermis in the head region is from the neural crest cell , in other words: from ectomesenchyme tissue. Ectodermal cells thicken into 4 layers by 11-12 weeks so at first the epidermis is from one layer then it is start to form more than one layer to give the epithelium which has Basal ,intermediate and superficial layer. Melanocytes -pigment cells from neural crest cells- invade epidermis. that is why they should be located within the epidermis to give pigmentation to the skin, from ectomesenchyme but later on they invade the epithelium to be located within the basal layer of the epithelium.

Structures developing from a combination of dermal and epidermal tissues, we have a number of structures that develop through an interaction between epithelium and connective tissue (Combination of ectodermal and mesodermal tissue), these are:Mammary, sebaceous, salivary glands. Teeth, nails, hair. Development of connective tissue Connective tissue is particularly from somites. CN develop from somites as migrating from either side of neural tube Somites : Sclerotome 1. Which is the Medial portion of the somite which gives the connective mesenchymal cells. Osteoblasts form bone, chondroblasts form cartilage, fibroblasts form CT. Myotome forms:1. Skeletal muscles. 2. Smooth muscles & mesenteries (smooth muscles of GI track). Dermatome give:1. Dermis. 2. Visceral mesoderm lamina propria of GIT. GIT the lining of it is endoderm but below it we have the lamina propria wich is from the dermatome of the somites. Development of cartilage & bone Cartilage is the initial skeletal component that functions in: 1. Supporting the soft embryo. 2. Maintains its 3-D configuration. till now the embryo is very soft, dont have bones yet so we need to maintain its rigidity for that reason we need some form of skeletal component . Cartilage forms before the bone (primary cartilage which forms within the embryo to maintain its shape) Cartilage migrate to surround notochord forming spinal column. Cartilage growth

1.Appositional we have new layers form on the surface(layer by layer). 2.Interstitial proliferation & expansion of cells , ( the cells grow in size so the tissue gets bigger). Types of cartilage: Hyaline elastic fibrous cartilage. The primary cartilage is hyaline cartilage Primary cartilage that forms first within the body of the embryo to maintain the rigidity of its body. Two types of Bone formation:1. Intramembranous ossification: means the mesoderm becomes bone directly. 2. Endochondral ossification: the mesodermal tissue first becomes a cartilage then the cartilage grows to give the shape of that tissue and later on once the shape is established bone starts replace the cartilage. E.g. long bone So..bone formation that involves primary transitional cartilage is called endocondrial ossification. Bone formation that doesn't involve primary transitional cartilage is called Intramembranous ossification.

Where do we need to have Endocondral/intramembranouse ossification? If the type of the bone that we want to build is very complex we need Endocondral ossification, if the bone is very simple we need Intramembranouse. For example the base of the skull which has many details. Also the bone of the nose in the nasal cavity has complicated details, to be able to build these types of complex bones you need something intermediate to shape the bone and this is the role of cartilage, that is why you need a cartilage to grow and give the bone its 3D shape and once the shape is established the bone come to replace cartilage, but if u take the cranial bones Which is the flat bones of the brain they are very simple these are 2 plates of bone fused together, because of that it can form easily without cartilage. We need endocondral ossification in cases of details where : 1. we need complexity (bone growth is complex). 2. When growth is needed. Endo-chondral bone Formation Deposition of bone matrix on a pre-existing cartilage matrix

Mesenchymal tissue Endo-chondral ossification

Cartilage

Bone

The nasal area and the base of the skull are formed by Endo-chondral ossification. The mandible is formed by intamembranouse ossification. We need endocondral ossification when we need to provide growth ,as when we want to provide growth to the ramus of the mandible. Also the long bones(ulna, radius, humerus etc) we need these bones to become longer that is why at the ends of these bones we have what is called Epiphyseal plate which is a cartilaginous tissue that formed by endoconrial to provide more length to the bone, Achondroplasia When we dont have a prober cartilage formation in the body,for example: dwarfs, these people have normal growth of the trunk but have short limbs because they have insufficiency growth of the cartilage (a problem with the development of the cartilage) in these people the intramembranouse ossification is not affected but the endocondrial ossification is afficted so we can notice that dwarfs have normal head and trunk size but short limbs also these people have the midface area going toward back that is because of the development of the midface area grows anteriorly because of the formation of cartilage in the nasal cavity and in the synchondrosis which located in the base of the skull.

Epiphyseal growth Endo-chondral ossification in a long bone. At the end of the long bone we have the Epiphyseal plate this era between the epithesis and diapithes, this era is very active and responsible for the continues growth and lengthening the bones people who have achondroplasia this area is inactive so they remain short. Development of muscle: By 10th week the myoblasts migrate from myotomes of the somites to form different types of muscles (Skeletal, smooth and cardiac). Development of Cardio Vascular System Originates: from angioblasts cells (from mesoderm). Angioblasts are from angiogenic clusters in the walls of the yolk sac Angiogenic clusters consist of :

1. Outer cells give elongating tubes ( blood vessels). 2. Inner cells give blood cells. Nutrition of embryo at first is from vatelline vascular system ,Then the embryo develops his own umbilical vascular system , the Heart start to beat by 4th week , it Starts as a tube then it get internal partitioning to form the atrium and ventricle. An opening between atria remain until birth normally should fused together, if it didnt fuse this will developed a problem that will easily fixed by a surgery. DEVELOPMENT OF OROFACIAL REGION(Lecture 2) Branchial Arches: By the age of 21 days the embryo starts to develop what we called bars in the lower jaw area or in lower part of the face and also in the neck region of the embryo. The buccopharengeal membrane rupture at the age of 21 days, it's located at the bottom of this cavity which is called Stomodeum (primitive mouth).

The end of that primitive mouth is a membrane this is actually the oropharengeal membrane ( buccopharengeal) which was originally the prochordal plate . this cavity remains separate from beginning of digestive system until the age of 21 days when this ruptures it is establishes communication btween the two cavities . Lets go back to the branchial arteries as we said we have grooves between the brachial arteries from outside these are branchial clefts. The first branchial cleft occurs between the first arch and the second brachial arch and so on. Usually the cleft is below the arch of the same number. Also there will be grooves from inside which are called pouches.

The branchial arches:The embryologic basis of all differentiated structures of the head and neck. We have five pairs of brachial arteries that start to appear on day 22 . Correspond to the primitive vertebrae gill bars , the fishes dont have branchial arteries they have what we called the gills ( )or the gill bars but in mammals they develop to form different structures in the head and neck region. Each arch consists of 3 layers:1. Overlying Outer covering of ectoderm. 2.Inner covering of endoderm. 3.Middle core of mesenchyme. Arches are separated further into:1.External, ectoderm-lined pharyngeal clefts. 2.Internal, endoderm-lined pharyngeal pouches. So the clefts are lined by ectoderm from outside and lined by endoderm from inside. Each branchial arch has :1. Skeletal elements. 2. Nervous elements. 3. Muscular elements. 4. Vascular elements. The first branchial arch :The most important arch in dentistry (very important to know , there will be more than 5 questions in the exam about this topic).

The skeletal element:Meckle`s cartilage , we have it in the right side and in the left side, the anterior part of Meckle`s cartilage dosent form the body of the mandible , some people say that because this cartilage located in the lower jaw region its form the body of the mandible but it is wrong because the body of the mandible formed by intramembranous ossification . - The role of Meckles cartilage: We need a cartilage in the mandible region to guide the development of the body of the mandible to act as scaffold thats mean to provide framework against which the body of the mandible forms. Notice that the body of the mandible forms at the lateral part of meckles cartilage , but meckeles cartilage doesnt become the body of the mandible . Meckle`s cartilage its a transient section that guide the formation of the body of the mandible and then disappear . The middle part of Meckle`s cartilage forms two ligaments :1. Anterior malleolar ligament which one of the ligaments that attach the malleus ( )one of the ossicles of the ear. 2. Sphenomandibular ligament which attach the mandibale to the spine of sphenoid . Now the dorsal end, Meckels cartilage has 3 parts: 1. Anterior part. 2. Midle part. 3. Posterior/dorsal. The dorsal part is the only part that remains and becomes the malleus, so the first ear ossicle(malleus) is formed by the ossification of the distal end part of Meckel`s cartilage. Q: Meckelscartilage ossify to give the following bone (1)Malleus (2)the body of mandible

We have another cartilage called Pterygoquadrate bar cartilage; small cartilage which gives the Incus- the second ear ossicle. Both cartilages occur in the first brachial arch. Meckel`s cartilage is important in guiding the formation of the body of the mandible the anterior part the middle part the perchondrum of the middle part becomes the anterior part of Anterior malleolar ligament and Sphenomandibular ligament, just the outer membrane makes the ligament not the whole cartilage. And the Dorsal end ossifies to make the Malleus(the first ear ossicle). Skeletal elements of the second arch- Reicherts cartilage. the dorsal end ossifies to make Stapes which is the last ear ossicle.

Remainder- forms Styloid process and stylohyoid ligament and Hyoid bone(not the whole bone;all bone except greater horn). Third arch has Greater horn of hyoid. So hyoid forms by 2 branchial arches: the body of hyoid bone is from the second arch while the greater horn is formed by third arch. Fourth to sixth arches forms the following cartilages are formed; Thyroid,cricoid and arytenoid cartilages. Nervous elements Each branchial arch has one specific nerve The nerve of First arch is Trigeminal nerve (V). The nerve of the second arch is Facial nerve (VII). The nerve of the Third arch is Glossopharungeal (IX). The nerves of the Fourth to sixth arches are Vagus nerve (laryngeal branches). These are cranial nerves which they are 12 in number. So... any muscle that innervated by Trigeminal nerve should developed in the first arch. First arch

*Muscles innervated by trigeminal nerve (1st arch) are Muscles of mastication(we will talk about this later). Second arch

*Muscles innervated by facial nerve are Muscles of facial expression. Third arch

* Glossopharyngeal nerve supplies only one muscle which is the Pharyngeal muscles that is why this muscle develops in the third arch. Fourth to sixth arches

*Muscles innervated by the laryngeal branches of Vagus nerve are the muscles of the top plate except tensor veli palatini, muscles of the pharynx and all muscles of larynx. We have digastrics muscle this muscle has 2 bellies;1. Anterior belly is supplied by the trigeminal nerve 2. Posterior belly is supplied by the facial nerve, so the gastric muscle is developed in 2 arches( the 1st and the 2nd arches). Similarly the hyoid bone develops in 2 arches 2nd and 3rd arches. Vascular elements We said that each arch has right & left aortic arch vessel. They lead from the heart and ascends dorsally to the face, brain & posterior region of the body. Third arch vessel becomes prominent to take over the facial region of the first two that is why it becomes the common carotid artery Fourth arch vessel is the dorsal aorta. Q: Stapidial artery is the vascular element of: The 2nd arch. Blood supply for neck & face Before week seven this region is supplied by internal carotid but after week seven by external carotid.

The end of the lecture, Done by: Mais Massarwi. Yara Ashqr. Rawan Enaia. Good luck