Medical Embryology - 2nd and 3rd Weeks Germ discs and Gastrulation Langman’s Medical Embryology, 11th Ed Chapter concepts 1. Bilaminar and Trilaminar germ discs 2. Origin of the three embryonic “germ’ layers that make up the trilaminar disk 3.Describe the formation and derivatives of ectoderm, mesoderm and endoderm Ⅰ. Gastrulation (Day 14 through Day 19) - Formation of Mesoderm, Endoderm and Ectoderm - At the caudal end, a midline indentation forms the primitive streak on the epiblast surface. - At the cranial end of the primitive streak is a slightly elevated region called the primitive node or knot which surrounds a small primitive pit. - Cells of the epiblast proliferate and migrate toward and down through the primitive streak in a process called invagination. - These invaginated cells subsequently detach and migrate underneath the epiblast. - Some cells displace hypoblast cells to become the intra-embryonic endoderm. - Other cells take residence between the developing intra-embryonic endoderm and the epiblast to become the intra-embryonic mesoderm. - Following the completion of gastrulation the epiblast layer is renamed the intra-embryonic ectoderm. ** NOTE The epiblast, through the process of gastrulation gives rise to all three germ layers in the developing embryo -Migration through the primitive streak continues until the end of the 4th week. -The primitive streak then undergoes regressive changes and disappears. -Distribution of intra-embryonic mesoderm -invaginating cells which became intra-embryonic mesoderm spread both laterally and cranially - at prochordal plate (oropharygeal membrane) and cloacal membrane, two region of fused epiblast and underlying hypoblast. -Formation of the notochord - cells invaginating in through the primitive pit or knot form a solid rod of mesoderm, the notochord, that migrates cranically until it abuts the oropharygeal membrane. - The notochord serve as the basis of the axial skeleton in the midline and establishes right and left orientation. -Changing shape of the germ disc - The embryonic disc is initially flat & round (Frisbee shaped) - It expands cranially and laterally to resemble a pear with subsequent elongation. **NOTE: development and differentiation is usually more advanced at the cranial end of the embryo when compared to more caudal structures, thus during the middle of the 3rd week, the cranial mesoderm and ectoderm have already begun to differentiate into specific entities which will be discussed later. Ⅱ.Differentiation introduction a. Beginning of the third week--Gastrulation ensues transforming the bilaminar disc into a trilaminar disc composed of ectoderm, mesoderm and endoderm. b. Between the 3-8th weeks the growing gestation is called an embryo. During the “Embryonic period” the major body form and organ structure take shape. External and internal features become recognizable as human. c. The seven months following this period (the fetal period), the growing gestation is now called a “fetus” and development focuses on maturing the newly formed organs and tissues to a functional state. Ⅲ Ectoderm Differentiation a. Neuralation - Ectoderm overlying the notochord, thickens to form the neural plate. - Lateral edges of the neural plate curve upward forming neural folds with a central neural groove. - Neural folds fuse at the future neck then progress cranially and caudally forming the neural tube, the future brain (cranial) and the spinal cord. - The anterior/rostral neuropore is the cranial opening of the neural tube, and the caudal opening- the posterior/caudal neuropore. - The anterior neuropore closes around day 25, the posterior neuropore around day 27. - Malformation can be associated with the closure of the anterior (anencephaly) or posterior (meningomyeloecel) neuropores. b. Neural crest - Cells at the “crest” of the neural folds detach and migrates as the fold fuse. - These cells called neural crest cells migrate throughout the body to provide intermediate neural like cells to a variety of tissues, forming two lines of cell cords- ganglion. c. In summary, the ectoderm will give rise to 1) The central nervous system (CNS): brain and spinal cord 2) Neural crest cells will give rise to melanocytes, ganglion (PNS) Note: In general terms it may be stated that the ectodermal germ layer gives rise to those organs and structures that maintain contact with the outside world: (a) the central nervous system (b) the peripheral nervous system (c) the sensory epithelium of the ear, nose and eye (d) the epidermis, including the hair and nails. In addition it gives rise to: the subcutaneous glands, the mammary gland, the pituitary gland, and the enamel of the teeth. Ⅳ Mesoderm Differentiation - initially loose - condensation day 17 - Paraxial mesoderm, adjacent to the developing neural tube a) Cranial to caudal segmentation of the paraxial mesoderm => somites 20th days, 3 pairs /per day, 42-44 pairs by the end of 5th weeks b) Subsequent recognization and differentiation of somites into 3 region: 1. Sclerotome—ventral; surrounding the developing neural tube and notochord=>vertebra 2. Myotome—will develop into the musculature of the region 3. Dermatome—dorsal; dermis of the overlying skin Note of Figure: Successive stages in the development of the somite. (a) The mesoderm cells are arranged around a small cavity. (b)The cells of the ventral and medial walls of the somite lose their epithelial arrangement and migrate in the direction of the notochord. These cells are collectively referred to as the sclerotome. (c) The dorsal somite wall gives rise to a new cell layer, the myotome. (d) After extension of the myotome in a ventral direction, the dermatome cells lose their epithelial configuration and spread out under the overlying ectoderm to form the dermis. - Intermediate mesoderm -kidneys and genital system “Urogenital tissue” - Lateral plate mesoderm - Separated by an intra-embryonic cavity=>the intra-embryonic coelom into 1. Outer layer—Somite/parietal mesoderm, lines the parietal layer of the body wall (pleura, peritoneum, pericardium) 2. intra-embryonic cavity—subdivided into peritoneal, pleural and pericardial cavities 3. Inner layer—Splanchnic/visceral mesoderm, forming muscle, CT of gastrointestinal system, visceral layer of pleura, peritoneum and pericardium. - Mesenchyme: formation of blood and vessels Ⅴ Derivatives of endoderm - The Gastrointestinal Tract - During formation of the secondary yolk sac, proliferation and migration of the endodermal germ layer has provided an inner endodermal lining. - Folding of the developing embryo incorporates a portion of the yolk sac into the embryo to form a endodermally lined tube - The head and tail folds incorporate the foregut and hindgut, respectively - The lateral folds produce the midgut which maintains contact with the yolk sac through the vitelline duct. -Associated Organs - Besides the gastrointestinal system, this endodermal tube will also contribute to the development of associated organs including 1) From the foregut: Thymus, Thyroid and parathyroid, Eustachian tubes and tympanic membrane, Lung, Liver & Pancreas 2) From the midgut: None 3) From the hindgut: Bladder and urethra Ⅵ. Folding of the Trilaminar Embryonic Disc a) During gastrulation cells are programed to become specific tissues. These cells then migrate to specific locations within the embryonic disc. b) Coordinated folding of the flattened disc is required to bring together these tissues to resemble the adult morphology. Some key landmarks 1. Oropharyngeal membrane - cranial fused 2 layered region (ectoderm and endoderm) limiting the notochord => will become the future mouth 2. Cardiogenic region - cranial to the oropharyngeal membrane => will become the future heart and ventral chest 3. Septum transversum - most cranial portion of disc => will subdivide the embryo and contribute to the diaphragm and liver 4. Cloacal membrane - caudal fused 2 layered region (ectoderm and endoderm) will become the future anus and genital openings - Neuralation and cerebral development causes a uneven distortion of the developing neural tube along the cranial-caudal axis a) Cerebral development causes the cardiogenic region and the oropharyngeal membrane, to fold ventrally b) Similar caudal folding flips the cloaca and tissue to the cloaca ventrally inverting their orientation - Somite and lateral plate mesoderm formation distorts the lateral aspects of the embryonic disc 1. This lateral folding pinches off a tube of the yolk sac to internalize the primitive gut 2. A transient connection with the yolk sac remains as the vitelline duct - The complicated folding process puts the developing embryo in a vulnerable position making it susceptible to drugs that may change migration rates, cell proliferation or cell adhesion - Clinical note of interest - by the end of the second month (8 wks) the form or malformation of the embryo is established. Some young mothers may not even know they are pregnant yet. Ⅶ Summary - During the embryonic period (3-8 weeks) the organs and the body shape are established - During this time the embryo is extremely sensitive to factors that can alter cell proliferation, cell adhesion and cell migration. - Chemicals that alter this balance and produce malformations are called teratogens. SUMMARY The embryonic period extends from the fourth to eighth weeks of development and is the period that each of the three germ layers gives rise to its own tissues and organ systems. As a result of the organ formation the major features of the body form are established. The ectodermal germ layer gives rise to those organs and structures that maintain contact with the outside world: (a) central nervous sysytem; (b) peripheral nervous sysytem; (c) sensory epithelium of ear,nose,and eye; (d) skin, including hair and nails;(e) in addition, the pituitary, mammary, and sweat glands as well as the enamel of the teeth are ectodermal derivatives. Each of these systems will be discussed in separate chapters. A most important component of the mesodermal germ layer is formed by the somites, which gives rise to the myotome (muscle tissue), sclerotome (cartilage and bone), and dermotome(subcutaneous tissue of the skin) which are all supporting tissues of the body. The mesoderm also gives rise to the vascular sysytem, that is, the heart, arteries, veins, lymph vessels, and all blood and lymph cells. Furthermore, it gives rise to the urogenital sysytem- kidneys, gonads, and their ducts (but not the bladder). Finally, the spleen and suprarenal glands are mesodermal derivatives. The endodermal germ layer provides the epithelial lining of the gastrointestinal tract, respiratory tract, and urinary bladder. It further forms the parenchyma of the tonsil, thyroid, parathyroids, thymus, liver, and pancreas. Finally, the epithelial lining of the tympanic cavity and Eustachian tube are lined by epithelium of endodermal origin. Body form. As a result of the formation of the organ systems and the rapid growth of the central nervous system, the initial flat embryonic disc begins to fold in cranio-caudal direction, thus establishing the head and tail folds. The disc also folds in a transverse direction, thus establishing the rounded body form. Connection with the yolk sac and placenta is maintained through the vitelline duct and umbilical cord, respectively.