Embryonic Development: Week 2

• The trophoblast is a thin layer of cells that aids embryo attachment to the uterine wall, protects the embryo, and contributes to the formation of the placenta

Week 2 (Days 7-14)

• The syncytiotrophoblast penetrates the epithelium and invades the endometrial connective tissue during blastocyst attachment
• The inner cell mass differentiates into the dorsal epiblast and ventral hypoblast, forming the bilaminar layer
• The amniotic cavity forms between the epiblast and cytotrophoblast
• The epiblast cavitates to form the amnion, an extra-embryonic epithelial membrane covering the embryo and amniotic cavity, eventually forming the body of the embryo
• The hypoblast proliferates, creating Heuser's membrane (primitive yolk sac), which nourishes the developing embryo until placenta formation
• The syncytiotrophoblast invades the endometrium and forms anastomosis with maternal blood sinusoids, creating trophoblastic lacunae for nutrient and waste exchange
• The syncytiotrophoblast produces hCG, a glycoprotein hormone that enters maternal blood and indicates pregnancy
• By day 9, the embryo is nearly completely implanted in the uterine endometrium, with a coagulation plug on the wall
• Extraembryonic mesoderm originates from the hypoblast/yolk sac and fills the space between the cytotrophoblast with the primitive yolk sac and amnion
• The extraembryonic mesoderm splits into splanchnic mesoderm (coating the outside of the primitive yolk sac) and somatic mesoderm (lining the inside of the cytotrophoblast)
• The space between the two layers of extraembryonic mesoderm is the chorionic cavity
• The somatic mesoderm fuses with the cytotrophoblast to form the chorion, which develops into the future placenta
• The splanchnic mesoderm wraps around the amniotic cavity and yolk sac to form the amnion
• A second wave of hypoblast proliferation forms the definitive yolk sac, pushing the primary yolk sac away, which then degenerates
• By the end of week 2, the definitive yolk sac loses contact with the remnants of the primary yolk sac
• The extraembryonic mesoderm becomes a thick connecting stalk suspending the bilaminar embryonic disc with its amnion and yolk sac in the chorionic cavity
• The connecting stalk develops into the umbilical cord, which forms a connection between the placenta and embryo

Week 2 Summary

• The implanted embryo becomes more deeply embedded in the endometrium
• There is the development of the bilaminar embryo, amniotic cavity, chorionic cavity, and yolk sac
• Trophoblast further develops into the placenta, with the syncytiotrophoblast forming anastomosis with maternal blood sinusoids and the cytotrophoblast combining with extraembryonic mesoderm

Week 3

• Week three is the embryonic period
• During the embryonic period, the formation of the three germ layers takes place

Body Axes and Trilaminar Layers

• The primitive streak is a thickened linear band that appears at the caudal part and moves towards the cranial part of the embryo, originating from epiblast cell proliferation toward the median plane
• The primitive node is a round, oval-shaped structure forming at the cranial end of the primitive streak, helping to establish the longitudinal axis of the embryo
• The appearance of the primitive streak allows the identification of the embryo's cranial-caudal axis
• The appearance of the primitive streak marks the start of gastrulation

Gastrulation

• Epiblast cells ingress along the primitive streak
• Increasing cells displace the hypoblast and form the definitive endoderm
• Other ingressing cells migrate between the epiblast and endoderm to form the mesoderm
• Ingressing cells replace the pre-existing epiblast to form the ectoderm
• The conversion from bilayer to trilaminar structure brings cell subpopulations into proximity so that they can undergo inductive interactions, which then patterns the layers and further differentiates them into specific tissues during embryonic development

Paths of Mesoderm Migration during Gastrulation

• Cranial mesoderm migrates straight towards the cranial region and is composed of cardiogenic mesoderm that moves to the future position of the oropharyngeal membrane
• Paraxial mesoderm moves slightly lateral from the midline and acts as the precursor tissue for paired somites near the neural tube
• Intermediate mesoderm migrates in a more caudal part and differentiates into organs of the urogenital system
• Lateral plate mesoderm moves laterally from the caudal part of the primitive streak and splits into somatic and splanchnic (intraembryonic) mesoderm as coelomic vesicles develop
• Somatic mesoderm will form the body wall
• Splanchnic mesoderm forms body cavities and the lining of internal organs and forms the bones/skeleton
• The two layers of intraembryonic mesoderm continue to develop and migrate outwards, eventually connecting with the extraembryonic mesoderm

Notochord Formation

• The oropharyngeal membrane is the future site of the oral cavity
• The cloacal membrane develops into the openings of the urogenital tract and the primordial anus
• The ectoderm and endoderm layers are fused at both membrane sites, which prevents mesoderm proliferation
• Prechordal mesoderm is the first population of mesoderm that arrives caudal to the oropharyngeal membrane, important in the formation of the craniofacial skeleton
• Prechordal mesoderm acts as a signaling center by releasing molecular signals which influences the development of surrounding tissues
• Mesoderm extends cranially from the primitive node to form the notochordal process, marking the beginning of notochord development
• The prechordal mesoderm and notochordal process are located in the midline of the mesoderm, and are components of axial mesoderm

Notochordal Process and Notochord

• A cavity forms within the notochordal process and results in the creation of a hollow tube
• A transient stage occurs where the notochordal process fuses with the underlying endoderm, with these fused layers gradually degenerating over time and leading to openings in the floor of the notochordal process, which creates a connection between the amniotic cavity and yolk sac and allows temporary exchange of nutrients between the two cavities
• The notochordal process transforms into the solid, rod-like notochord as the embryo continues to develop and cells migrate to the same region
• In adulthood, the notochord is replaced by the vertebral column/spine, yet remnants can still be found in nucleus pulposus
• The Notochord induces the following:
• Formation of nucleus pulposus in adulthood
• Formation of other structures of the CNS during embryonic development

Week 3 Summary

• There is the formation of primitive streak
• Gastrulation leads to the formation of the trilaminar embryo
• There is the Formation of notochord

Three Germ Layers

• Ectoderm layers are the most external and have more contact with the external environment
• The mesoderm is between the endoderm and ectoderm
• The Endoderm such as pleural and peritoneal linings of cavities + liver have more contact with the internal environment

Ectoderm Derivatives: Nervous System Development

• The notochord and prechordal mesoderm induce the overlying ectoderm to form a neural plate (neuroectoderm), initiating neuralation as the notochord forms a neural tube
• The notochord further induces the neural plate to invaginate along its central axis to form a longitudinal median neural groove, which has neural folds on each side
• By the end of the 3rd week, the neural folds have begun to move together and fuse, converting neural plates into the neural tube, which is the primordium of the brain ventricle and spinal cord
• As neural folds meet, the neural tube separates from the surface ectoderm
• During tube formation, neural crest cells migrate away and separate into left and right paired parts that shift to the dorsolateral aspects of the neural tube
• Neural crest derivatives:
• Some sensor and postganglionic portions of PNS
• Adrenal medulla
• Melanocytes of skin
• Connective tissues of head Induction of the neural plate occurs at the occipitocervical region, so the neural tube is connected with the amniotic cavity
• The anterior neuropore is an opening located at the head region of the developing embryo
• The posterior neuropore is an opening of the neural tube at the caudal end
• Under normal circumstances, the anterior neuropore closes earlier than the posterior neuropore

Mesoderm Derivatives

• Paraxial mesoderm derivatives are:
• Medial part (sclerotome): Forms vertebrae and ribs
• Middle part (myotome): Forms skeletal muscles
• Lateral part (dermatome): Forms dermis of skin
• The somites form in pairs along the neural tube
• Intermediate mesoderm derivatives are:
• Organs and tissues of the urogenital system and parts of the genital system
• Lateral plate mesoderm turns into bones and muscles

Endoderm Derivatives: Digestive Tract

• Initially, the embryo is a flat disc-shaped structure with the prominent neural tube running along the midline

Cranial-Caudal Fold

• During weeks 3-4, the embryo grows rapidly and folds around the yolk sac
• The head region elevates and folds ventrally towards the midline, with the tail region concurrently folding ventrally
• The endoderm incorporates into the folding process to form a tube-like structure within the embryo, continuing until the head and tail region meet in midline to form a complete tube-like/cylindrical structure
• The completed tube develops into the GI tract later

Lateral Body Folding

• Lateral body folding is initiated by rapidly growing somites and lateral plate mesoderm
• The lateral edge of the embryonic disc bends sharply towards the median plane, causing edges of the embryonic disc to fold ventrally so a roughly cylindrical embryo forms
• The amniotic cavity surrounds the entire embryo simultaneously and exerts pressure on the yolk sac
• The yolk sac transforms into the tube-like primitive gut while maintaining the endodermal lining
• Body folding plays an important role in internalizing the endoderm
• Folding process completion results in formation of a gut tube from endoderm
• Gut tube starts at the stomodeum (primitive mouth region) to the cloaca (primitive anus)
• The tube can differentiate into various organs at specific regions
• The endoderm gives rise to derivatives:
• Pharyngeal pouches
• Epithelial lining of lung buds and trachea
• Liver
• Gallbladder
• Pancreas