human organism starting with the fusion of the sexual gametes until the 8th week of the intrauterine life. Embryogenesis follows three distinctive stage : 1. Premorfogenesis – segmentation of the zygote into blastomeres, giving birth to the morula and the blastocyst 2. Primordial morphogenesis – achieved by gastrulation, thus forming the embrionic layers : the ectoblast, the mezoblast and the endoblast, forming the gastrula. 3. Secondary morfogenesis – from the three embryonic layers which are forming the future organs. The chronological display of the embryogenesis , starting with the fertilized egg stage or the zigote stage presumes : 1. The segmentation of the zygote, which is transforming into morula. 2. Blastocistogenesis which forms the uni-, bi- and trilaminar blastocist, at the same time with the implantation process – the blastocist nesting into the uterine mucosa. 3. Gastrulation which forms the 3 embryonic layers. Neurulation, characterised by the primitive neural tube and neural crests formation. During its intrauterine development the new formed organism is known as concept or product concept. Starting with the fertilization moment until the first division the term used is egg or zygote. In primele trei saptamani de dezvoltare, numite si perioada preembrionara conceptul este numit preembrion. Intre saptamanile 4-8 dupa fecundatie, numita si perioada embrionara apar schitele primelor organe si conceptul capata aspect uman, numindu-se embrion. During the first three weeks of development , also knows as the preembrionic period, the concept is known as preembryo. Between the 4th and the 8th week after fertilization 9 weeks human embyo Starting with the 3rd month of the intrauterine life the embryo becomes a fetus, owing to the process of organogenesis Preembrionic stage (week 1-3)
The human zygote, resulted from the ovocite
fertilization by the sperm, begins the segmentation process. Through this process it forms 2-4-8 cell divisions. Once the zygote reached the two-cell stage it follows a series of mitotic divisions that lead to a rapid development of the cell number. These cells that in turn become smaller with every division are known as blastomeres. After 3 to 4 divisions, the zygote turns into morula. This stage is developed after 3 days following the fertilization, and the embryo is ready to enter the uterus. The morula is constituted from a group of cells with an outer coat and an external one. The internal coat forms the embryonic tissues while the external coat forms the trophoblast which subsequently contributes to the placenta formation. Blastocyte formation By the time the morula enters the uterus the liquid starts to penetrate zona pellucida in the intercellular space of the internal coat. Thus the intercellular spaces become confluent and form a unique cavity, the blastocele. The internal coat cells are localized at one of the poles, while the external coat cells flatten and form the epithelial wall of the blastocyst. The zona pelucida disappears thus permitting the beginning of the implantation. Bilaminar Germ Disc (Second Week of Development)) At the eighth day of development the blastocyst is partially embedded in the endometrial stroma (3). In the area over the embryoblast, the troophoblast has differentiated into two layers: (a) an inner layer of mono-nucleated cells, the cytotrophoblast, and (b) an outer, multinucleated zone without distinct cell boundaries, the syncytiotrophoblast or syncytium. Implantation of the zygote and the layers of the germ disc. The cells of the inner cell mass or embryoblast also differentiate into two layers: (a) a layer of small, cuboidal cells, known as the hypoblast layer; and (b) a layer of high columnar cells, the epiblast layer. The cells of each of the germ layers form a flat disc and together they are known as the bilaminar germ disc.. At the same time a small cavity appears within the epiblast. This cavity enlarges to become the amnionic cavity. . By the 13th day of the embryonic stage, the cells of the cytotrophoblast proliferate locally and penetrate into the syncytiotrophoblast, thus forming cellular columns surrounded by syncytium. The cellular columns with the syncytial covering become known as the primary stem villi.. In the meantime, the endodermal germ layer produces additional cells that migrate along the inside of the exocoelomic membrane. These cells proliferate and gradually form a new cavity within the exocoelomic cavity. This new cavity is known as the secondary or definitive yolk sac In acelasi timo, celomul extraembrionar se extinde si formeaza cavitatea corionica. Meanwhile, the extra-embryonic coelom expands and forms a large cavity known as the chorionic cavity. The extra-embryonic mesoderm lining the inside of the cytotrophoblast is then known as the chorionic plate. The only place where extra-embryonic mesoderm traverses the chorionic cavity is in the connecting stalk. With the development of blood vessels, the stalk will become the umbilical cord. By the end of the second week, the germ disc is represented by two apposed cell discs: the epiblast, which forms the floor of the continuously expanding amniotic cavity, and the hypoblast, which forms the roof of the secondary yolk sac. In its cephalic region the hypoblastic disc shows a slight thickening known as the prochordal plate. Blastocyst - day 13
1. Secondary yolk sac
2. Exocoelomic cyst 3. Aminotic cavity 4. Extra-embryonic coelom 5. Epiblast 6. Connecting stalk 7. Hypoblast 8. Primary villi 9. Trophoblastic lacunae 10. Extraembryonic somatic mesoderm 11. Extraembryonic splanchnic mesoderm Trilaminar Germ Disc (Third Week of Development) The most typical event occurring during the third week is the formation of the primitive streak on the surface of the epiblast. Firstly the streak is vaguely defined, but in a 15- to 16- day embryo it is clearly visible as a narrow groove with slightly bulging regions on either side. The cephalic end of the streak, known as the primitive node, consists of a slightly elevated area surrounding a small pit. In a transverse section through the region of the primitive groove it is seen that the cells are flask-shaped and that a new cell layer develops between the epiblast and hypoblast . It is now generally believed that cells of the epiblast migrate in the direction of the primitive streak to form the mesoderm and probably a portion (if not all) of the intraembryonic endoderm. On arrival in the region of the streak, they become flask-shaped, detach from the epiblast and slip underneath it. This inward movement is known as invagination. Once the cells have arrived between the epiblast and hypoblast, they form an intermediate cell layer, known as intra-embryonic mesoderm. This is the mesodermal or third germ layer and its establishment is known as gastrulation. As more and more cells move in between the epiblast and hypoblast (gradually they migrate beyond the margin of the disc and establish contact with the extra-embryonic mesoderm covering the yolk sac and amnion in the cephalic direction,) they pass on each side of the prochordal plate to meet each other in front of this area, where they form the cardiogenic or heart forming plate Formation of Notochord The cells invaginating in the primitive pit move straight forward in cephalic direction until they reach the prochordal plate. In this manner they form a tube-like process, known as the notochordal or head process. The small, central canal is considered as the forward extension of the primitive pit. With further development the notochordal cells proliferate and form a solid cord, known as the definitive notochord. This structure in turn becomes detached from the endoderm, which once again forms an continuous layer in the roof of the yolk sac. The notochord forms now a midline axis, which will serve as the basis of the axial skeleton. It extends from the prochordal plate (the future buccopharyngeal membrane) to the primitive node. A small canal, the neurenteric canal, temporarily connects the yolk sac and the amniotic cavity. Alongside with the formation of the cloacal membrane, the posterior wall of the yolk sac forms a little diverticulum which extends into the connecting stalk. This diverticulum, the allantoenteric diverticulum, or allantois, appears at about the 16th day of development. Even though in some lower vertebrates the allantois serves as a reservoir for the excretion products of the renal system, in man it remains rudimentary and plays no role in development. Notochord and the layers of the germ disc. Notochord formation Notochord formation Growth of Germ Disc The embryonic disc, at first flat and almost round, gradually becomes elongated with a broad cephalic and a narrow caudal end. Expansion of the embryonic disc occurs mainly in the cephalic region; the region of the primitive streak remains more or less the same size. It must be realized, however, that growth and elongation of the cephalic part of the disc are caused by a permanent migration of cells from the primitive streak region in a cephalic direction. Invagination of surface cells in the primitive streak and their subsequent migration in forward and lateral directions continue until the end of the fourth week. At that stage, the primitive streak shows regressive changes, quickly diminishes in size, and soon disappears. It is, however, not unusual that remnants of the primitive streak persist and at birth cause tumors in the sacrococcygeal region. These tumors often contain tissues derived from all three germ layers. Bilaminar disc layers Embryonic Period (Fourth to Eighth Week) Throughout the fourth to eighth week of development, a period known as the embryonic period, all of the three germ layers gives rise to a number of specific tissues and organs. By the end of the embryonic period the main organ systems have been established. As a consequence of the organ formation, the shape of the embryo changes seriously and the major features of the external body form are recognizable by the end of the second month. At the same time with the formation of the notochord, and in all probability under its inductive influence, the ectoderm overlying the notochord gives rise to the central nervous system. The neural plate, steadily expands toward the primitive streak. By the end of the third week the lateral edges of the neural plate become more elevated to form the neural folds, while the depressed midregion forms a groove, the neural groove. Gradually the neural folds come close to each other in the midline, where they fuse. This fusion begins in the region of the future neck (fourth somite) and proceeds in cephalic and caudal directions As a consequence, the neural tube is formed. At the cephalic and caudal ends of the embryo the tube remains for the moment in open connection with the amniotic cavity by way of the anterior and posterior neuropores, respectively Neural plate formation Somites formation Germ layers derivative The ectodermic germinative layer forms the organs and the structures that maintain contact with the environment : 1. Central nervous system 2. Peripheral nervous system 3. Sensory epithelium of ear, nose and eye. 4. Skin, including hair and nails 5. The pituitary, mammary and sweat glands, enamel of the teeth. A very important component of the mesodermal germ layer is formed by the somites, which give rise to the myotome (muscle tissue), sclerotome (cartilage and bone) and dermatome (subcutaneous tissue) which are all supporting tissues of the body. The mesoderm also gives rise to: 1. The vascular system. 2. The urogenital system. 3. Spleen. 4. Suprarenal glands. The endodermal germ layer gives rise to: 1. The gastrointestinal tract 2. The respiratory tract 3. Urinary bladder 4. Tonsils, thyroid, parathyroid, thymus, liver, pancreas 5. Tympanic cavity, Eustachian tube. The germ layers derivatives Special embryology Organogenesis The Skeletal System The skeletal system develops from the mesenchyme. The flat bones of the skull undergo a membranous ossification when the mesenchyme cells are transformed into osteoblasts. In the long bones of the limbs the mesenchyme is condensing and is forming the hyaline cartilage. The ossification centers appear in the cartilage models and the bone ossifies due to the endochondral ossification. The ribs and the vertebral column develop from the sclerotome compartments of the underlying sclerotome. The Muscular System The muscular system has a mesodermal origin. Most of the skeletal muscules are derived from the myotome that is providing the myoblasts for the multinucleated muscle fibers. The head and neck muscles originate from the branchial arch mesoderm. The smooth muscles and the cardiac mucle fibers are derived from splanchnic mesoderm. The Cardiovascular System The heart, blood vessels and blocd cells are derivative of the mesodermal germ layer. The central position of the cardiogenic area is located initially anterior to the prochirdal plate and the neural plate. By the 22th day of development the cardiac tubes form a single bent heart tube. This tube consists of an inner endocardial tube and a surrounding epimyocardial mantle. Between the fourth and the seventh week of development, the heart is divided into a typical four – chambered structure. In atrium, a crest descending from the roof of the atrium leaves a lumen “ostium primum” for communication between the atrium. Later, a septum secundum is formed. Only at birth the two septa are pressed one against the other and the communication is closed due to the increased pressure in the left atrium. The interventricular septum consists of a thick muscular part and a thin membranous part. Cardiac arches formation Atrial and ventricular septum formation The Digestive System The epithelium of the digestive system is of endodermal origin and the muscular along with the peritoneal components are of mesodermal origin. This system extends from the buccopharyngeal membrane to the cloacal membrane. The digestive system in embryo is divided into: 1. Foregut 2. Midgut 3. Hindgut 1.Foregut 5.Pancreas 2.Thyroid 6. Midgut 3.Lung 7. Hindgut 4.Stomach The foregut forms the esophagus, the trachea, the lung buds, the stomach, the proximal duodenum and bile duct, the liver, the pancreas. The midgut forms the primary intestinal loops , the distal duodenum. The primary loop protrudes by the 6th week into the umbilical cord- physiological herniation and by the 10th week it returns into the abdominal cavity; during this period it is rotating 270 ° counterclockwise. The hindgut forms the region between the distal 1/3 of the transverse colon to the upper part of the anal canal. The caudal part of the hindgut is divided by the urorectal septum into the rectum and anal canal posteriorly and urinary bladder and urethra anteriorly. Lesser and greater The primitive gout omentum formation formation The Nervous System The central nervous system is of ectodermal origin. At the beginning it is formed by the neural plate, who’s edges become folded, these neural folds approach each other in the midline to fuse into the neural tube. The CNS forms a tubular structure with a broad cephalic portion, the brain, and a long caudal portion, the spinal cord. The brain forms the cranial part of the CNS and consists originally of three brain vesicles : 1. The rhombencephalon. 2. The mesencephalon. 3. The prosencephalon or forebrain. CNS components The Limbs The limb buds become visible at the beginning of the 5th week as a paddle shaped buds. At the apex of the buds the covering layer of the ectoderm is thickened and is known as the apical ectodermal ridge. By the 6th week of development, the terminal portion of the buds become flattened – hand and foot plates. While the external shape is being established, the mesenchyme in the buds begins to condense and by the 6th week of development the hyaline cartilage models can be recognized. Limb bud formation