Organogenesis (Weeks 3-8) - PDF

Organogenesis 1 Dr. Prince LM Zilundu College of Medicine Ajman University [email protected]  Lecture objectives Understand the key germ layers formed from gastrulation Know the key structures derived from the 3 germ layers Understand the role of...

Organogenesis 1 Dr. Prince LM Zilundu College of Medicine Ajman University [email protected]  Lecture objectives Understand the key germ layers formed from gastrulation Know the key structures derived from the 3 germ layers Understand the role of the primitive streak and notochord Understand the process of neurulation Understand the concept of lateral body and cephalocaudal folding Understand the development of the lateral mesoderm. Understand its association with the body cavities and blood islands Understand the development of endoderm and how the communication between the gut-tube & the structures of the umbilical cord Recap: First Week of Development 1: oocyte immediately after ovulation; 2: fertilization, 12-24h after ovulation; 3: Male and female pronuclei stage 4: First mitotic division; 5, two-cell stage (30 hours of age) 6: Morula containing 12 to 16 blastomeres (3 days of age); 7: Advanced morula stage reaching the uterine lumen (4 days of age); 8: Early blastocyst stage (approximately 4.5 days of age; the zona pellucida has disappeared); 9: Early phase of implantation (blastocyst approximately 6 days of age). 6 to 8 Week 2: IMPLANTATION Zona pellucida disintegrates Trophoblast cells near uterine wall express L-Selectin & Integrins Uterine epithelium expresses receptors for L-selectin L-Selectin + receptors=blastocyst attaches to uterus (capture) Integrins attach to extracellular laminin & fibronectin = then invades & begin to implant  Syncytiotrophoblast Uterine gland Cytotrophoblast Week 2: IMPLANTATION & BILAMINAR DISC Amniotic cavity Fate of Trophoblast Maternal capillary Cytotrophoblast o Inner layer: mononucleated cells o Active mitosis to grow syncytiotrophoblast Syncytiotrophoblast o Outer, multinucleated cells o No active mitosis o Contribute to placenta Hypoblast Fate of Inner cell mass (embryoblast) Epiblast Differentiate into a flat disc (bilaminar disc: o Epiblast o Hypoblast Blastocyst cavity becomes yolk sac Organogenesis the process of formation of body form & organs from three germ layers. 3rd to 8th week Involves: o gastrulation o cell-cell interaction, o cell fate determination, o cell proliferation and survival, o cell and tissue shape and size, and "Carnegie stage," which consists of 23 stages, ranging from stage o arrangement of cells into tissues & 1 (fertilized egg) to stage 23 (8 weeks after fertilization) o ultimately functional organs. Week 2 Changes (bilaminar disc) to Week 3 (trilaminar disc: gastrulation) Gastrulation: Formation of 3 Primary Germ Layers Steps: 1. Appearance of the primitive streak o proliferation & migration of epiblast cells to the median plane of the embryonic disc o Streak gets grooved and its cranial end forms primitive node (Hensen's) o Cells leave deep surface of primitive streak to form ENDODERM & MESODERM up to end of Week 4 o Forms intraembryonic mesoderm, notochord, septum transversum, determines craniocaudal axis & Left/Right of embryo o Fate: becomes a vestigial structure in sacrococcygeal region  Underoges degeneration/disappears 2. Development of the notochord o primary inductor in the early embryo 3. Differentiation of three germ layers o (ectoderm, mesoderm, endoderm) Gastrulation: Formation of 3 Primary Germ Layers Steps: 1. Appearance of the primitive streak 2. Development of the notochord (3-4 Weeks) Formed by cells that migrate cranially from the primitive node and pit Lies in the midline, between ectoderm & endoderm Between primitive streak & prochordal plate Defines the axis of the embryo and gives it some rigidity Stimulates the development of the axial skeleton (such as the bones of the head and vertebral column) induces the overlying embryonic ectoderm to thicken and form the neural plate (CNS primordium) Indicates the future site of the vertebral bodies Notochord persist as the nucleus pulposus 3. Differentiation of three germ layers (ectoderm, mesoderm, endoderm) Gastrulation: Formation of 3 Primary Germ Layers Steps: 1. Appearance of the primitive streak 2. Development of the notochord 3. Differentiation of three germ layers (ectoderm, mesoderm, endoderm) Ectoderm o outside world ▪ structures of the nervous system, sensory receptors and skin epidermis, hair, nails, enamel of teeth Mesoderm o structure of the body ▪ muscles (smooth & skeletal), bones, connective tissues, blood & the circulatory system, urogenital systems, body cavities Endoderm o inside world ▪ epithelial linings of the digestive, respiratory and accessory organs of gut Gastrulation Week 3-4 sacrococcygeal teratoma Start with formation of Primitive Streak (groove, pit & node) Epiblast migrate towards primitive streak Invagination of epiblast – o actively form mesoderm & o endoderm epiblast  Migrating endoderm displaces hypoblast Cells remaining in epiblast are now called ectoderm Primitive streak regress (wk 4) o Failure to regress lead to sacrococcygeal teratoma Notochordal process & Prechordal plate Buccopharyngeal membrane o future mouth Cloacal membrane o caudal to primitive streak (future anus) At these points, both ectoderm & endoderm membranes (no mesoderm) fused to prevent further migration of germ cells mesoderm Week 3-4 Neurulation Formation of neural tube Neural tube becomes brain & spinal cord Steps of Neurulation: 1. Neuroectoderm Formation: Ectoderm cells above the notochord (inducer) differentiate into neuroectoderm. 2. Neural Plate Forms: Neuroectoderm cells create a thick neural plate. Extends from prochordal plate to the primitive node (knot) 3. Neural Groove and Folds: Plate margins rise, forming a neural groove & folds. 4. Neural Tube Formation: Folds fuse at midline, forming the neural tube. Neural crest cells also formed Cranial tube forms the brain (Forebrain, Midbrain & Hindbrain) Caudal tube forms the spinal cord. Week 3-4 Neurulation in the Clinic Neural tube o becomes brain & spinal cord Fusion of the neural folds o proceeds in cranial and caudal directions until only small areas of the neural tube remain open at both ends The cranial opening o the rostral neuropore— closes on approximately the 25th day The caudal neuropore o closes 2 days later Closure of the neuropores o syndecan4 and Vangl2 are involved in this process. Specialisation of Intraembryonic Mesoderm Mesoderm -Fills space between ectoderm & endoderm on either side of neural tube -Divide into 3 parts: 1. Paraxial Mesoderm: Condenses next to the neural tube. 2. Intermediate Mesoderm: Located between paraxial and lateral mesoderm; intermediate in position and thickness. 3. Lateral Mesoderm: Thin layer on the lateral side of the embryonic disc paraxial mesoderm Divides into 2 by extraembryonic coelom.  Lateral Plate/Splanchnic/visceral: covering of lateral mesoderm visceral organs (visceral pleura & peritoneum) (somatic/parietal part) lateral mesoderm (somatic/parietal part) inner lining of body walls (parietal pleura & peritoneum); dermis of skin; connective tissue of limbs lateral mesoderm (splanchnic/visceral part)  Transverse sections showing development of the mesodermal germ layer The mesodermal sheet gives rise to: 1. paraxial mesoderm (future somites) 2. intermediate mesoderm (future excretory units), 3. lateral plate, which is split into: parietal mesoderm visceral mesoderm Lateral and Cephalocaudal Folding what happens to the germ layers? Development of blood and blood vessels. Week 3 A. The umbilical vesicle (yolk sac) and a portion of the chorionic sac (at approximately 18 days). B. Dorsal view of the embryo exposed by removing the amnion. C. C to F, Sections of blood islands, showing progressive stages in the development of blood and blood vessels. chorion & connecting stalk cardiogenic region placenta circulatory system Cardiovascular system Vessels of the gut, portal system of gut & liver  Extraembryonic Membranes & Placenta Extraembryonic membranes o are amnion, yolk sac, allantois, chorion, placenta, and umbilical cord are responsible for protection, respiration, excretion, and nutrition of embryo and fetus. At birth, placenta, umbilical cord, and other extraembryonic membranes are separated from the fetus and expelled from uterus as an afterbirth WHAT IS THE DIFFERENCE BETWEEN: o Intraembryonic mesoderm o Extraembryonic mesoderm Implantation and Placentation After implantation of the blastocyst, the functional layer of the endometrium of the uterus is termed decidua. Decidual reaction: syncytiotrophoblast starts secreting human chorionic gonadotrophin (HCG) o stromal cells enlarge, vacuolate, and get filled to the brim with glycogen and lipids The decidua is divided into: o Decidua basalis: lies deep to the embryo & contributes to the placenta. o Decidua capsularis: forms a capsule around the embryo & separates it from the uterine cavity. o Decidua parietalis: Rest of the decidua (excluding decidua basalis and decidua capsularis) is termed decidua parietalis Formation of chorion frondosum & chorion laeve Small finger-like projections (chorionic villi) form around the chorionic sac. Villi near decidua capsularis compress and degenerate, creating a smooth area called chorion laeve. Villi near decidua basalis grow extensively, forming the chorion frondosum. Formation of trabeculae and intervillous spaces Trophoblast: o Syncytiotrophoblast rapidly expands, erodes decidua basalis, forming lacunae (small cavities).​ o Formation of trabeculae and intervillous spaces Lacunae grow and form trabeculae (villous primordia) around the developing embryo.​ Lacunae merge, creating blood-filled intervillous spaces surrounding each trabeculum. The following three types of villi develop in succession: Primary Villi: o Cytotrophoblast forms finger-like projections surrounded by syncytiotrophoblast. Secondary Villi: o Extraembryonic somatopleuric mesoderm invades the villus, forming three layers: mesoderm, cytotrophoblast, syncytiotrophoblast. Tertiary Villi: o Blood vessels form in the mesoderm, creating the vascularized tertiary villus.  Anchoring Villi Formation  Cytotrophoblast cells form a shell separating the syncytiotrophoblast from decidua basalis. Anchoring Villi:  Villi attach to both chorion (fetal side) and decidua (maternal side). Main trunk (Truncus chorii), branches (Ramus chorii), and sub-branches (Ramuli chorii).  Offshoots grow into intervillous spaces as free villi. Intervillous Space: Becomes a ‘bag of vascular sponges’ with new villi formation. The placental membrane is made up of five layers. From the maternal side to fetal side these are: 1. Syncytiotrophoblast 2. Cytotrophoblast (up to 20 weeks) 3. Basement membrane of cytotrophoblast 4. Mesoderm in the core of villus 5. Endothelium and basement membrane of fetal capillaries.  1 Primitive groove 2 Primitive pit 3 Primitive node 4 Oropharyngeal membrane 5 Cardiogenic plate 6 Sectional edge of amniotic membrane 7 Mesoderm 8 Endoderm 9 Future cloacal membrane NB 1+2+3 primitive streak Extra information: derivatives of the three germ layers: -ectoderm, -endoderm, & -mesoderm Fourth Week Development: Major body changes; The embryo has 4 to 12 somites. Day 24: First pharyngeal arches visible; heart prominence forms and pumps blood. Day 26: Three pairs of pharyngeal arches visible; rostral neuropore closes; C-shaped curvature forms. Days 26-27: Upper limb buds, otic pits (ears), and lens placodes (eyes) appear. End of week: Lower limb buds and tail-like caudal eminence visible; rudiments of organ systems established.  somites the presomitic (unsegmented) paraxial mesoderm becomes segmented to form epithelial somites. These form two initial subdivisions: sclerotome and dermamyotome; later, the dermamyotome forms the myotome + dermis Sclerotome makes vertebrae and ribs What about the notochord?_______________________________ Fifth Week Development Head Growth: Rapid brain development enlarges the head. o Due to rapid development of the brain and facial prominences Facial Development: Face contacts heart prominence. Pharyngeal Arches: Second arch overgrows third and fourth, forming cervical sinus. Mesonephric Ridges: Indicate site of developing temporary kidneys (mesonephric kidneys). Urogenital system (5-6 weeks) Intermediate mesoderm = urogenital ridge= genital ridge + nephrogenic ridge/cord Genital ridge forms_______________ Gonads Nephrogenic cord forms____________________ Kidneys  Sixth Week Development Movement & Reflexes: Embryo shows spontaneous movements and reflex responses to touch. Limb Development: Upper limbs: Elbows and hand plates with digital rays form. Lower limbs: Develop slightly later, showing similar differentiation. External Ear Formation: Auricular hillocks around pharyngeal groove form the auricle (external ear). Eye & Head Changes: Eyes become prominent due to retinal pigmentation. Head grows larger and bends over heart prominence. Umbilical Herniation: Intestines temporarily herniate into the umbilical cord due to limited abdominal space.  Sex differentiation into male/female gonads happens Limb Development: Seventh Week Notches form between digital rays, defining fingers and toes. Gut & Yolk Stalk: Communication reduces; yolk stalk becomes the Development: omphaloenteric duct. Ossification: Bone formation begins in upper limbs.  the lateral plate mesoderm gives rise to the bones, ligaments, tendons, and dermis of the limbs. Limbs 5-8weeks In contrast, the limb muscles and endothelial cells migrate into the developing limb bud from the somites endochondral ossification Eighth Week Highlights: Digits fully separated; limb regions defined. Scalp vascular plexus forms around the head. Purposeful limb movements begin. Primary ossification starts in femora. Caudal eminence disappears; hands and feet meet ventrally. Embryo shows human characteristics; large head and defined neck. Eyelids unite; intestines remain in umbilical cord. External genitalia show slight sex differences. alimentary system (digestive system)  Pre-embryo (Blastocyst) Inner Cell Mass Trophoblast   Epiblast & Hypoblast Syncytiotrophoblast & Cytotrophoblast    Ectoderm  skin, nervous system etc Placenta Chorionic sac Mesoderm paraxial  dermatome  dermis of skin  myotome skeletal muscles  sclerotome axial skeleton intermediate  urogenital (urinary & reproductive) system lateral  somatic  parietal pleura & peritoneum etc  splanchnic  visceral pleura & peritoneum etc blood islands  heart & blood vessels Endoderm  digestive tract and accessory organs 44 Larsen's Human Embryology Gary C. Schoenwolf, PhD University of Utah School of Medicine Salt Lake City, Utah Steven B. Bleyl, MD, PhD University of Utah School of Medicine Salt Lake City, Utah Philip R. Brauer, PhD Creighton University School of Medicine Omaha, Nebraska Philippa H. Francis-West, PhD King's College London Dental Institute London, United Kingdom FIFTH EDITION