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embryology developmental biology human development medical science

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This document contains detailed notes on general embryology, covering the germinal, embryonic, and fetal periods of human development. It explains key processes like cleavage, implantation, gastrulation, and the formation of germ layers, in addition to trophoblast and inner cell mass differentiation, and the development of extraembryonic membranes.

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IAS33: General Embryology I. Introduction to Embryonic Development Embryonic development is a highly orchestrated process involving the transformation of a single fertilized cell into a complex, multi-cellular organism. This process is divided into distinc...

IAS33: General Embryology I. Introduction to Embryonic Development Embryonic development is a highly orchestrated process involving the transformation of a single fertilized cell into a complex, multi-cellular organism. This process is divided into distinct periods: Germinal Period (Weeks 1-2): Characterized by fertilization, cleavage, and implantation. Embryonic Period (Weeks 3-8): Marked by gastrulation, neurulation, and organogenesis. Fetal Period (Weeks 9-38): Involves growth and maturation of established structures. These periods are crucial as they lay the foundation for the formation of all major organs and tissues in the body. II. Germinal Period (Weeks 1-2) A. Formation and Implantation of the Blastocyst Early Cleavage Stages: After fertilization, the zygote undergoes a series of rapid cell divisions called cleavage. These divisions produce smaller cells (blastomeres) without increasing the overall size of the embryo. Morula Stage: As cleavage continues, a solid ball of cells known as the morula (composed of about 16 to 32 cells) is formed. This stage occurs approximately 3-4 days after fertilization. Fluid Accumulation: As the morula develops, fluid begins to accumulate in the intercellular spaces between the blastomeres. This fluid is derived from the uterine IAS33: General Embryology 1 environment and is pumped into the morula by the cells. Formation of the Blastocoel: The accumulation of fluid leads to the formation of a central cavity called the blastocoel. The cells continue to pump fluid into this cavity, causing it to expand. Blastocyst Structure: As the blastocoel expands, the structure reorganizes into a hollow sphere known as the blastocyst. Blastocyst Formation: About five days after fertilization, the embryo reaches the blastocyst stage. A blastocyst consists of: Inner Cell Mass (ICM): A group of cells that will develop into the embryo itself. Trophoblast: An outer layer of cells that will form part of the placenta, facilitating nutrient and waste exchange between the mother and the embryo. Attachment to Uterine Wall: The blastocyst attaches to the endometrial lining of the uterus, initiating implantation. B. Differentiation of Inner Cell Mass and Trophoblast Once implantation begins, the cells of the blastocyst start to specialize into different types. IAS33: General Embryology 2 Trophoblast Differentiation: The outer trophoblast differentiates into two cell types: Cytotrophoblast Definition: The inner layer of the trophoblast composed of mononucleated cells. Functions: Proliferation: Acts as a reservoir of proliferative cells that continuously divide and contribute to the growth of the trophoblast. Migration: These cells migrate into the outer layer, forming the syncytiotrophoblast. Syncytiotrophoblast Definition: A multinucleated layer formed by the fusion of cytotrophoblast cells. Key Features: Invasive Properties: Exhibits behavior similar to cancer cells, allowing for the invasion of the uterine epithelium. Hormone Secretion: Produces essential hormones, including human chorionic gonadotropin (hCG), which supports pregnancy by maintaining the corpus luteum and regulating maternal physiology. IAS33: General Embryology 3 The syncytiotrophoblast invades the maternal tissue, creating spaces known as trophoblastic lacunae, which fill with maternal blood. Finger-like Projections: The syncytiotrophoblast forms projections that extend into the lacunae, covering a core of cytotrophoblast cells. These structures are known as primary villi, acting as the site of nutrient absorption and waste removal. 1. Inner Cell Mass (ICM) Differentiation: The ICM — embryoblast differentiates into two layers: Epiblast (Dorsal Layer): This layer will give rise to the embryo itself, forming all the tissues and organs of the body. Hypoblast (Ventral Layer): Contributes to the formation of extraembryonic structures, such as the yolk sac, which provides nutrients to the growing embryo. C. Formation of Bilaminar Germ Disc Bilaminar Structure: The ICM forms a bilaminar (two-layered) germ disc composed of the epiblast and hypoblast. IAS33: General Embryology 4 1. Amniotic Cavity Formation: A fluid-filled space called the amniotic cavity forms between the epiblast and the cytotrophoblast. This cavity will surround and protect the developing embryo. 2. Yolk Sac Formation: The hypoblast creates a membrane known as Heuser’s membrane, forming the primitive yolk sac. The yolk sac serves as an early source of nutrients until the placenta is fully developed. D. Formation of Amniotic and Chorionic Cavities IAS33: General Embryology 5 Amniotic Cavity: Provides a protective fluid-filled environment for the developing embryo. Chorionic Cavity: Forms as the extraembryonic mesoderm splits into two layers, creating a space between the somatic mesoderm and splanchnic mesoderm. E. Development of Extraembryonic Mesoderm Extraembryonic Mesoderm Formation: Begins around day 9-13 as cells migrate to fill the space between the cytotrophoblast and primitive yolk sac. Layer Differentiation into the Chorionic Cavity: Splanchnic Mesoderm: Lines the primitive yolk sac and will form parts of the circulatory system and internal organs. Somatic Mesoderm: Contacts the cytotrophoblast and contributes to the formation of the body walls and limbs. Somatic Mesoderm + Cytotrophoblast = Chorion → Placenta F. Formation of a Definitive Yolk Sac A second wave of hypoblast cells proliferation produces a new membrane pushing the primary yolk sac in front of it, forming the definitive yolk sac. The primary yolk sac is pushed away towards the other end of the chorionic cavity. Degenerates into a collection of vesicles. IAS33: General Embryology 6 G. Splitting of the Primary Yolk Sac and the Definitive Yolk Sac Expansion of the choronic cavity A population of extraembryonic mesoderm resides, becoming a connecting stalk that suspends the developing embryo in the chorionic cavity Develop into the embryonic cord, which serves as a connection between the placenta and the embryo IAS33: General Embryology 7 III. Embryonic Period (Weeks 3-8) A. Gastrulation Gastrulation is the process by which the developing embryo transforms from a two-layered structure into a three-layered one, forming the trilaminar embryonic disc. 1. Primitive Streak Formation: IAS33: General Embryology 8 Definition: The primitive streak is a thickened linear band of cells that forms in the epiblast layer of the embryonic disc during the gastrulation phase of embryonic development. Location: It appears caudally (toward the tail end) of the embryonic disc and extends toward the cranial (head) end. It establishes the body axis of the embryo. Formation Process: The primitive streak arises from the proliferation and inward movement (ingression) of epiblast cells toward the median plane of the embryonic disc. This migration is critical for organizing the future body plan of the embryo. Significance: Gastrulation: The primitive streak marks the beginning of gastrulation, a process where the three germ layers (ectoderm, mesoderm, and endoderm) are formed. Cell Differentiation: Cells that migrate through the primitive streak will differentiate into various tissues and organs of the developing embryo. IAS33: General Embryology 9 Establishment of Body Axes: It plays a key role in determining the anterior-posterior (head-to-tail) axis and the left-right asymmetry of the embryo. 2. Primitive Node: Description: A small, rounded structure at the anterior end of the primitive streak. Role: Acts as a signaling center for axis formation and gastrulation. 3. Formation of Three Germ Layers: 1. Epiblast Proliferation and Ingression: IAS33: General Embryology 10 Description: The process begins with the proliferation of epiblast cells at the primitive streak. Ingression: Cells from the epiblast migrate inward, moving into the space between the epiblast and hypoblast layers. 2. Formation of the Endoderm: Displacement of Hypoblast: As epiblast cells ingress, they displace the hypoblast cells, leading to the formation of a new layer called the endoderm. 3. Formation of the Mesoderm: Migration of Ingressing Cells: Other cells that ingress during this process migrate between the newly formed endoderm and the remaining epiblast to create the mesoderm. 4. Formation of the Ectoderm: Displacement of Epiblast: The cells that ingress will displace the pre- existing epiblast, resulting in the formation of the ectoderm. Function of Germ Layer Formation The primary function of this process is to bring together subpopulations of cells, enabling them to undergo inductive interactions that pattern the germ layers. This interaction is crucial for the further differentiation of these layers into specific tissues during embryonic development. Germ Layer Derivatives Ectoderm: Description: The outermost layer. Derivatives: Forms the nervous system (including the brain and spinal cord) and the skin (epidermis). Mesoderm: Description: The middle layer. IAS33: General Embryology 11 Derivatives: Gives rise to muscles, bones, the circulatory system, and other connective tissues. Endoderm: Description: The innermost layer. Derivatives: Forms the gastrointestinal tract, respiratory systems, and associated organs (e.g., liver, pancreas). B. Formation and Differentiation of the Intraembryonic Mesoderm The intraembryonic mesoderm differentiates into three primary subdivisions: paraxial mesoderm, intermediate mesoderm, and lateral plate mesoderm. Each of these sub-types plays a crucial role in the formation of specific tissues and organs in the developing embryo. IAS33: General Embryology 12 1. Cranial Mesoderm: Location: Oropharyngeal membrane Derivatives: Cardiogenic mesoderm. 2. Paraxial Mesoderm: Location: Slightly lateral from the midline. Forms somites, which later differentiate into: Sclerotome: Develops into vertebrae and ribs. Myotome: Forms skeletal muscles. Dermatome: Gives rise to the dermis of the skin. Connection to Intraembryonic Mesoderm: As a component of the intraembryonic mesoderm, the paraxial mesoderm is essential for axial skeleton development and muscle formation. 3. Intermediate Mesoderm: Location: Migrate in a caudal direction, between the paraxial mesoderm and lateral plate mesoderm. Derivatives: Urogenital system components, including kidneys and repoductive gonads. Connection to Intraembryonic Mesoderm: As another subdivision of the intraembryonic mesoderm, the intermediate mesoderm is critical for developing the urinary and reproductive systems. 4. Lateral Plate Mesoderm: IAS33: General Embryology 13 Location: Laterally from the caudal part of the primitive streak. Coelomic Vesicles: Forms coelomic vesicles that give rise to body cavities. Connection to Intraembryonic Mesoderm: The lateral plate mesoderm, as part of the intraembryonic mesoderm, is essential for establishing body cavities and the development of the circulatory system. Splits into: Somatic Mesoderm: Forms body walls and limbs. Splanchnic Mesoderm: Lines body cavities and forms the heart and blood vessels. 💡 This intraembryonic mesoderm originates from the developing embryo itself, unlike the extraembryonic mesoderm that splits to form the chorionic cavity. The intraembryonic mesoderm (somatic and splanchnic) continue to develop and migrate outward, eventually connecting with the extraembryonic mesoderm. Oropharyngeal and Cloacal Membranes IAS33: General Embryology 14 The oropharyngeal and cloacal membranes are critical structures that help delineate the boundaries of the developing embryo and prevent mesodermal invasion in specific areas. 1. Oropharyngeal Membrane: Location: Situated at the cranial end of the embryo. Function: This membrane is formed by the fusion of ectoderm and endoderm and marks the future site of the mouth. As development progresses, this area will contribute to the formation of the oral cavity and associated structures. 2. Cloacal Membrane: Location: Found at the caudal end of the embryo. Function: Similar to the oropharyngeal membrane, the cloacal membrane forms through the fusion of ectoderm and endoderm. It will eventually give rise to the openings of the urogenital and anal tracts, playing a key role in the development of the lower digestive and excretory systems. C. Notochord Formation The notochord is a crucial structure that plays an essential role in embryonic patterning and axis formation. IAS33: General Embryology 15 Prechordal Mesoderm Position: Located just caudal to the oropharyngeal membrane. Role: Acts as a signaling center for craniofacial development, influencing surrounding tissues through molecular signals. Notochordal Process Development: Arises from cells migrating through the primitive node. Initially forms as a hollow tube known as the notochordal process. Transformation: The process undergoes significant changes, including the formation of a cavity, resulting in a hollow tube when viewed in cross-section. Notochord Development IAS33: General Embryology 16 Fusion with Endoderm: Around day 18, the notochordal process temporarily fuses with the underlying endoderm, creating a transient structure that forms openings between the amniotic cavity and the yolk sac. Significance: Although the function of this transient stage is not fully understood, it facilitates temporary nutrient exchange. Final Structure: Eventually, the notochordal process solidifies into the notochord, a rod-like structure crucial for axial development and signaling. IAS33: General Embryology 17 Role of the Notochord Inductive Functions Central Nervous System Development: The notochord emits signals that are vital for the induction and patterning of the neural tube, the precursor to the central nervous system. Axial Skeleton: It serves as the primary skeletal support in the embryo before being replaced by the vertebral column. Adult Remnants Nucleus Pulposus: In adults, remnants of the notochord are found in the nucleus pulposus of intervertebral discs, acting as a gelatinous core that provides flexibility and cushioning between vertebrae. D. Body Folding and Gut Tube Formation Body folding transforms the flat embryonic disc into a three-dimensional structure, crucial for internal organ formation. 1. Body Folding: a. Cranial-Caudal Folding: IAS33: General Embryology 18 The embryo’s initial shape: A flat disc shaped structure with a prominent neural tube running along the midline Process: Folding of the head and tail regions ventrally towards the midline during weeks 3-4. Concurrently, the tail region of the embryo folds ventrally (to the underside). The endoderm is incorporated into the folding process and forms a tube-like structure within the embryo. Folding continues until the head and tail region meet in the midline, forming a complete tube-like structure. IAS33: General Embryology 19 Result: Formation of the gastrointestinal tract from the endoderm. b. Lateral Body Folding: Process: Lateral edges of the embryonic disc fold towards the median plane. Edges of the embryonic disc folds ventrally, forming a roughly cylindrical embryo. The amniotic cavity surrounds the entire embryo and exerts pressure on the yolk sac, transforming into a tube-like structure (primitive gut) while maintaining the endodermal lining. Result: Formation of a cylindrical embryo with internalized endoderm. 2. Gut Tube Development: Formation: Endoderm folds to create the primitive gut tube, extending from the stomodeum (future mouth) to the cloaca (future anus). Differentiation: Specific regions of the gut tube will develop into various digestive and respiratory organs. IAS33: General Embryology 20 Week 3 Summary Primitive Streak Formation: Establishes the embryo's cranial-caudal axis and initiates gastrulation. Germ Layer Formation: The ectoderm, mesoderm, and endoderm arise, setting the foundation for all major tissues and organs. Notochord Development: A key event in organizing the body's axial structures and inducing central nervous system formation. IV. Neurulation IAS33: General Embryology 21 1. Induction of the Neural Plate Both the notochord and prechordal mesoderm induce part of the ectoderm to become a neural plate. Result: The ectoderm thickens above the notochord and prechordal mesoderm, forming the neural plate. The induction of the neural plate occurs at the occipitocervical region (neural tube is connected with the amniotic cavity) 2. Formation of Neural Groove and Folds The neural plate undergoes invagination along its central axis, creating a longitudinal median neural groove with neural folds on either side. IAS33: General Embryology 22 3. Fusion of Neural Folds Progression: By the end of the third week, the neural folds begin to elevate and move toward the midline, eventually converging and fusing to form the neural tube. Significance: This fusion establishes the primordium of the brain ventricles and the spinal cord. The neural tube separates from the surface ectoderm as the neural folds meet. 4. Migration of Neural Crest Cells IAS33: General Embryology 23 Neural Crest Formation: As the neural folds fuse, neural crest cells emerge from the edges of the neural plate. These cells migrate to the dorsolateral aspects of the neural tube. Derivatives: Neural crest cells give rise to: Sensory and postganglionic portions of the peripheral nervous system (PNS). Adrenal medulla. Melanocytes of the skin. Connective tissues of the head. 5. Neuropores and Their Closure Neuropore Locations: The anterior neuropore is located at the head region of the developing embryo. The posterior neuropore is located at the caudal end of the neural tube. Closure Timeline: The anterior neuropore closes around day 25 of development. IAS33: General Embryology 24 The posterior neuropore closes slightly later, around days 27-28. Significance: Proper closure of the neuropores is critical to prevent neural tube defects. V. Derivatives of Germ Layers — Organogenesis Fates of the Ectoderm Central Nervous System (CNS): Brain and spinal cord. Peripheral Nervous System (PNS): Nerves outside the CNS. Neural Crest Cells: Sensory neurons, melanocytes, facial cartilage. Epidermis: Skin, hair, nails. Special Sensory Organs: Eyes, ears. Neuroectoderm: Forms neural tube and nervous system structures. Fates of the Mesoderm Musculoskeletal system, circulatory system, internal organs. Fates of the Endoderm Digestive Tract: From mouth to the caudal part of the embryo (cloaca), forming the primitive anus. IAS33: General Embryology 25 Respiratory Tract: Lungs, trachea. Liver and Pancreas: Metabolic and digestive enzyme production. Gallbladder: Bile storage. Epithelial Linings: Urinary bladder, urethra. Summary Embryonic development is a complex, highly regulated process involving: 1. Germinal Period (Weeks 1-2): Formation and implantation of the blastocyst, differentiation into trophoblast and ICM, and establishment of extraembryonic structures. 2. Embryonic Period (Weeks 3-8): Gastrulation forming three germ layers, neurulation creating the nervous system, and body folding setting the stage for organogenesis. 3. Derivatives of Germ Layers: Ectoderm (nervous system, skin), mesoderm (musculoskeletal, circulatory systems), and endoderm (digestive, respiratory systems). 4. Regulation of Laterality: Establishment of left-right asymmetry through molecular signaling. IAS33: General Embryology 26 Timeline of Embryonic Development IAS33: General Embryology 27

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