EMBRYO-LC4 3rd to 8th Weeks PDF

o Mesoderm lines in trophoblast which rises from the hypoblast...

o Mesoderm lines in trophoblast which rises from the hypoblast TOPIC OUTLINE o Cavity adjacent to the epiblast → amniotic cavity o Cavity adjacent to hypoblast → yolk sac (blastocyst cavity) I. GASTRULATION II. FORMATION OF NOTOCHORD III. ESTABLISHMENT OF BODY AXES IV. 3RD TO 8TH WEEKS OF DEVELOPMENT: PERIOD OF ORGANOGENESIS A. Derivatives of the Ectodermal Germ Layer I. GASTRULATION I. Gastrulation Most characteristic event that occurs in the 3rd week of gestation is gastrulation. Gastrulation: formation of three germ layers: Figure 3. Implantation site at the end of second week o Endoderm (inner most layer) o Mesoderm (middle layer) o Ectoderm (outermost layer) Figure 1. The three germ layers. Figure 4. Representative view of the germ disc at the end of the second week of Begins with the formation of primitive streak (PS) on the surface of development. The amniotic cavity has been opened to permit a view of the the epiblast (ectoderm): cephalic end, primitive node, surrounding dorsal side of the epiblast. The hypoblast and epiblast are in contact with each primitive pit. other, and the primitive streak forms a shallow groove in the caudal region of The primitive streak is clearly visible as a narrow groove with slightly the embryo. bulging regions on either side at the caudal end of the embryonic disc; it appears in a 15- to 16-day embryo. The cephalic end of the streak, the primitive node, consists of a slightly elevated area surrounding the small primitive pit. By the end of the 4th week, the primitive streak shows regressive changes, rapidly shrinks and soon DISAPPEARS. The primitive streak is the first morphological sign of gastrulation located at the surface of the epiblast of the bilaminar embryonic disc. Figure 5. Dorsal view of an embryo showing the primitive node and streak and a cross section through the streak. Cells of the epiblast migrate toward the primitive streak. Upon arrival in the region of the streak, they become flask-shaped, detach from the epiblast, and slip beneath it. This inward movement is known as Figure 2. The primitive pit, node, and groove. invagination. Recall that: Invagination is controlled by fibroblast growth factor 8 (FGF8). o Trophoblast divides into two: syncytiotrophoblast and Fibroblast growth factor 8 (FGF8) cytotrophoblast - Controls cell migration and specification Page 1 of 5 [EMBRYO] 1.04&05 3rd TO 8th WEEK OF DEVELOPMENT– Dr. La Paz L. Peredo, MD - Synthesized by streak cells - Down regulating E-cadherin (a protein that normally binds epiblast cells together) - Controls cell specification into the mesoderm by regulating BRACHYURY (T) expression. Cells invaginate and displace the hypoblast, creating the endoderm. Between epiblast and new endoderm (that was produced previously) forms the mesoderm. Cells remaining in epiblast form the ectoderm. The epiblast cells continue to move laterally, cranially and caudally. Those epiblast cells that move cranially are formed into two: - Precordial plate which will be the induction of forebrain - Oropharyngeal membrane, the future opening of oral cavity Figure 8. Summary up to the formation of the new endoderm to mesoderm. Epiblast gives rise to all 3 germ layers in the embryo: ectoderm, Figure 6. Dorsal side of the germ disc from a 16-day embryo indicating the mesoderm, and endoderm (deepest). All these layers form all of the movement of surface epiblast cells [solid black lines] through the primitive tissues and organs during organogenesis. streak and node and the subsequent migration of cells between the hypoblast The primary villi, small capillaries, villous capillaries and the and epiblast [broken lines]. connecting stalk (chorionic plate) supply the embryo with nutrients and oxygen. Remember that the trophoblast will be the future placenta and this placenta will provide oxygen and nutrients to the embryo. In the cephalic direction, they pass on each side of the prechordal plate. Later, the prechordal píate will be important for induction of the forebrain. II. FORMATION OF NOTOCHORD Figure 7. Cross section through the cranial region of the streak at 15 days showing invagination of epiblast cells. The first cells to move Inward displace the II. Formation of Notochord hypoblast to create the definitive endoderm. Once definitive endoderm is The invaginating prenotochordal cells in the primitive node will move established, inwardly moving epiblast forms mesoderm. toward the cranial region in the midline, until they reach the prechordal plate. These cells become intercalated in the hypoblast so that for a short time, the midline of the embryo has two cell layers → notochordal plate. As the endoderm cells move in at the streak continue to replace the hypoblast, the notochordal plate cells proliferate and detach from the endoderm. This will now form a solid cord of cells, referred to as the definitive notochord, which underlies the neural tube, and serves as the basis for the axial skeleton. - The notochord and prenotochordal cells extend cranially to the prechordal plate (an area just caudal to the oropharyngeal membrane) and caudally to the primitive pit. At the point where the pit forms an indentation in the epiblast, the neurenteric canal temporarily connects the amniotic and yolk sac cavities. - The cloacal membrane is formed at the caudal end of the embryonic disc. When the cloacal membrane appears, the posterior wall of the yolk sac forms a small diverticulum that extends in the connecting stalk. This diverticulum, the allantoenteric diverticulum, or allantois, appears around the 16th day of development. Page 2 of 5 [EMBRYO] 1.04&05 3rd TO 8th WEEK OF DEVELOPMENT– Dr. La Paz L. Peredo, MD o In ECG (Electrocardiogram) the P,Q,R,S are significant for ventricular response. The heart is on the left, so it should be an upward wave on the left side and downward on the right. o But if there is an upward wave on the right and downward on the left, this is considered a dextrocardia; this should not be an exclusion for the patient not to be physically fit. - Situs solitus: in normal position - Situs inversus - if the organ is positioned in a reverse manner such as in a mirror image arrangement. For example, the organ that is supposedly on the right but is placed on the left and one that is placed on the left is placed on the right. - Situs ambiguous: has more than one abnormality located on the Figure 9. Drawing of a sagittal section through a 17-day embryo. The most opposite side. cranial portion of the definitive notochord has formed, whereas prenotochordal cells caudal to this region are intercalated into the FATE MAP ESTABLISHED DURING GASTRULATION endoderm as the notochordal plate. Note that some cells migrate ahead - Paraxial Mesoderm are those migrating at the lateral edges of the of the notochord. These mesoderm cells form the prechordal plate that node and from the cranial end of the streak will assist in forebrain induction. - Intermediate Mesoderm are cells migrating through the mid streak region - Lateral Plate Mesoderm forms those migrating through the more caudal part of the streak. - Cells migrating through the caudal most part of the streak contribute to extraembryonic mesoderm GROWTH OF EMBRYONIC DISC - initially flat and almost round, gradually becomes elongated, with a broad cephalic and a narrow caudal end. Growth and elongation of the cephalic part of the disc are caused by a continuous migration of cells from the primitive streak region in a cephalic Figure 10. Schematic cross section through the region of the notochordal plate. direction. At that stage, the primitive streak shows regressive Soon, the notochordal plate will detach from the endoderm to form the changes, rapidly shrinks, and soon disappears. definitive notochord. - That the primitive streak at the caudal end of the disc continues to supply new cells until the end of the fourth week has an important bearing on development of the embryo. - Thus, gastrulation, or formation of the germ layers, continues in caudal segments while cranial structures are differentiating, causing the embryo to develop cephalocaudally. IV. 3RD TO 8TH WEEK OF DEVELOPMENT: PERIOD OF ORGANOGENESIS IV. Period of Organogenesis Figure 11. Schematic view showing the definitive notochord. Formation of tissues and organs 3 germs layers: ectoderm, mesoderm, and endoderm, gives rise to a number of specific tissues and organs III. ESTABLISHMENT OF BODY AXES Ectoderm germ layer (everything that is in contact with the outside world) e.g. CNS, PNS, sensory epithelium of ear, nose, eye, skin, hair, nails, pituitary, mammary, and sweat glands III. Establishment of Body Axes - The central nervous system (CNS) Anterior- posterior AP cranio caudal, dorso-ventral DV, left-right - The peripheral nervous system (PNS) (LR) occurs early in embryogenesis, initiated during morula stage. - The sensory epithelium of the ear, nose and eyes. The AP axis forms the anterior visceral endoderm (AVE) at the - The epidermis, including the hair and nails. cranial end of the endoderm which will become the head region. - The subcutaneous glands Mesoderm will ventralize to contribute to kidneys in the presence - The mammary glands of FGF8, bone morphogenetic protein 4 (BMP4), transforming - The pituitary gland growth factor-β (TGF-β). - Enamel of the teeth Node is the organizer dictating which organ will be formed at that Mesoderm germ layer (tissues that support the body) e.g. time. somitomeres, myotome (muscle tissue), sclerotome (cartilage, bone), Nodal is involved in initiating and maintaining the primitive streak. dermatome (skin) Laterally (L-R sidedness) – primitive streak appears, FGF8 Endoderm germ layer (organs within the body) e.g. GIT, RT, UB, secreted, nodal expression restricted to L side. Abnormal thyroid, parathyroid, liver, pancreas, tympanic cavity, auditory tube expression includes laterality defects: situs inversus, dextrocardia. Induction of the neural plate caused by the upregulation of Organs are already formed during this week. Asymmetrical organs such Fibroblast Growth factor (FGF), inhibition of the activities of Bone as heart, stomach, pancreas, and spleen. Morphogenetic Protein 4 (BMP4), Transforming growth factor-β Lateral defects – abnormally expressed nodal expressions and are (TGF-β) controlled by the serotonin neurotransmitter. - Dextrocardia – the heart located on the right side is considered an abnormal expression. Page 3 of 5 [EMBRYO] 1.04&05 3rd TO 8th WEEK OF DEVELOPMENT– Dr. La Paz L. Peredo, MD Figure 13. Dorsal view of a 16-day presomite embryo. The primitive streak and primitive node are visible. Figure 12. The three germ layers and their derivatives. Formation of neural tube from neural plate (neurulation) - lengthening of neural plate and body axis (cranial to caudal) and body axis, lateral edges elevate to form neural folds and the depressed mid region form Figure 14. Dorsal view of an 18-day presomite embryo. The embryo is neural groove pear-shaped, with its cephalic region somewhat broader than its caudal Neural folds approach each other in the midline where they end. fuse in the cervical region, proceeds cranially and caudally → neural tube is formed NEURULATION - Folding and closure of the neural tube occurs first in the cervical region - The neural tube then ‘’zips” up toward the head and the tail, leaving two openings in which are the anterior and posterior neuropores. - The anterior neuropore closes around day 25. - The posterior neuropore closes around day 28. By the end of the third week, the lateral edges of the neural plate become elevated to form neural folds, and the depressed mid region forms the neural groove (Figure 16 and 17) Gradually, the neural folds approach each other in the midline, where they fuse (Figure 18 and 19) Figure 15. Dorsal view of an 18-day human embryo. Note the primitive Fusion begins in the cervical region (fifth somite) and proceeds node and, extending forward from it, the notochord. The yolk sac has a cranially and caudally; As a result, the neural tube is formed. somewhat mottled appearance. The length of the embryo is 1.25 mm, and Until fusion is complete, the cephalic and caudal ends of the the greatest width is 0.68 mm. neural tube communicate with the amniotic cavity by way of the anterior (cranial) and posterior (caudal) neuropores (Figure 18, 19, and 20 A) Closure of the cranial neuropore occurs at approximately day 25 (18- to 20-somite stage), whereas the posterior neuropore closes at day 28 (25-somite stage) (Figure 20 B) NEURULATION COMPLETE - narrow caudal portion → spinal cord - broader cephalic portion → brain vesicles Page 4 of 5 [EMBRYO] 1.04&05 3rd TO 8th WEEK OF DEVELOPMENT– Dr. La Paz L. Peredo, MD Figure 16. (A) Dorsal view of a late presomite embryo [approximately 19 days]. The amnion has been removed, and the neural plate is clearly visible. (B) Dorsal Figure 19. (C) Dorsal view of an embryo at approximately day 23. Note the view of a human embryo at 19 days. pericardial bulge on each side of the midline in the cephalic part of the embryo. (D) Dorsal view of a human embryo at 23 days. Figure 17. (A) Dorsal view of an embryo at approximately 20 days showing somites and formation of the neural groove and neural folds. (B) Dorsal view of a human embryo at 20 days. Figure 20. (A) A Lateral view of a 14-somite embryo (approximately 25 days). Note of the bulging pericardial area and the first and second pharyngeal arches. (B) The left side of a 25-somite embryo approximately 28 days old. The first three pharyngeal arches, lens, and otic placodes are visible. V. REFERENCES Sirmata trans Sadler, T.W. & Langman, J. (2012). Langman’s Medical Embryology (13th Ed). Wolter’s Kluwr Health / Lippincott Williams and Wilkins. Moore K. L. Persaud T. V. N. & Torchia M. G. (2008). The developing human : clinically oriented embryology (8th ed.). Saunders/Elsevier. Figure 18. (A) Dorsal view of an embryo at approximately day 22. Seven distinct somites are visible on each side of the neural tube. (B) Dorsal view of a human embryo at 21 days. 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