Week 2 reading

Chapter 4: Third week of human development

  • Gastrulation: A formative process by which the three germ layers, which are precursors of all embryonic tissues, and the axial orientation are established in embryos.

    • Bilaminar embryonic disc is converted into a trilaminar disc.

    • Gastrulation is the beginning of morphogenesis (development of body form) and is the move significant event during the 3rd week. The embryo is referred to as a gastrula.

  • Each of the three germ layers gives rise to specific tissues and organs:

    • Ectoderm: epidermis, central and peripheral nervous systemcs, eyes and internal ears, neural crest cells, and many connective tissues of the head.

    • Endoderm: epithelial linings of the respiratory and alimentary (digestive) tracts, including the glands and opening into the gastrointestinal tract, and glandular cells of associated organs such as the liver and pancreas.

    • Mesoderm: all skeletal muscles, blood cells, lining of blood vessels, all visceral smooth muscular coats, serosal linings of all body cavities, ducts, and organs of the reproductive and excretory systems, and most of the cardiovascular system.

  • The first morphologic sign of gastrulation is the formation of the primitive streak on the surface of the epiblast (related to amniotic cavity) of the bilaminar disc.

    • The thickened linear band of the epiblast appears caudally (tail end) in the median plane (down the middle) of the dorsal (towards the back) aspect of the embryonic disc.

    • The primitive streak results from proliferation and movement of cells of the epiblast to the median plane of the embryonic disc, where it becomes possible to identify the embryo’s craniocaudal axis, cranial and caudal ends, dorsal and ventral surfaes, and right and left sides.

    • It's cranial end proliferates to form the primitive node.

    • Basically, the epiblast cells proliferate and move towards the midline, creating the primitive streak.

    • At the cranial end of the primitive streak, cells proliferate and create the primitive node, which is like a small knob.

    • Concurrently, a narrow groove (like a trench), the primitive groove, develops in the primitive streak that is continuous with a small depression in the primitive node, the primitive pit.

    • Primitive streak develops primitive groove

    • Primitive node develops primitive pit

    • After the primitive streak appears, cells move beneath its surface to create mesenchyme, and loosely packed embryonic tissue, which acts as a supportive framework to form the body’s connective tissues and the supporting structures of glands.

    • Some mesenchyme cells develop into mesoblast, which goes on to form the intraembryonic mesoderm (the embryo’s middle germ layer).

    • Cells from the epiblast and primitive node displace the hypoblast (small cuboidal cells) forming the embryonic endoderm in the roof of the umbilical vesicle (yolk sac).

    • The cells remaining in the epiblast form the embryonic ectoderm.

    • The production of the mesoderm slows down and the primitive streak diminishes in the fourth week.

  • Notochordal process and notochord

    • Big picture: Cells move through primitive streak —> become mesoderm —> some form the notochord —> the notochord helps organize the embryo and signals the nervous system to develop.

    • Some mesenchymal cells move through the primitive node and migrate cranially, forming the notochordal process (long chord of cells running down the middle of the embryo).

    • The notochordal process then develops a hollow center called the notochordal canal.

    • Notochordal process: tube of cells

    • Notochordal canal: hollow space inside the tube

    • The notochordal process grows cranially until it reaches the prechordal plate (a small area where the ectoderm and endoderm are touching/fused. Normally, the mesoderm is going to come between the ectoderm and endoderm, but the prechordal and oropharyngeal regions (future oral cavity), and cloacal membrane are special places where it doesn’t.

    • The prechordal plate acts as a signaling center that helps organize the development of structures towards the head, like the forebrain, eyes, and other cranial structures.

    • Some mesenchymal cells with a mesoderm fate spread between the ectoderm and endoderm.

    • Some of those mesoderm cells migrate around the prechordal plate, meeting each other and forming cardiogenic mesoderm, where the heart primordium begins developing at the end of week 3.

    • Then the notochord is formed from the notochordal process. It establishes the embryo’s longitudinal axis (head to tail). It acts as a sigaling center for nearby tissues, like the ectoderm to form the neural plate, which is the beginning of the central nervous system.

    • The notochordal process develops a hollow center forming the notochordal canal, which fuses with the underlying ectoderm. This structure becomes a flattened sheet which is the notochordal plate. This then folds inwards, pinches off from the endoderm, and becomes the notochord.

    • The neurenteric canal is a temporary connection between the amniotic cavity and the umbilical vesicle that forms during remodeling of the notochordal process, then disappears.

    • The notochord is mostly temporary, but little pieces remain and become the nucleus pulposus, a portion of the intervertebral disc.

  • The allantois

    • Around day 16, a tiny pouch grows out of the caudal wall of the umbilical vesicle, called the allantois.

    • This extends into the connecting stalk, which is the early structure connecting the embryo to the chorion/placental region.

    • Its surrounding mesoderm helps form blood vessels serving the placenta, contributing to umbilical arteries.

    • Part of the allantois becomes associated with the bladder, and its proximal remnant becomes the urachus, a connection extending from the bladder towards the umbilicus. The urachus closes and becomes the median umbilical ligament.

  • Neurulation = making the neural tube

    • The notochord signals the ectoderm above it which becomes neural tissue. The ectoderm receiving these signals thicks and forms the neural plate. This is specialized ectoderm called the neuroectoderm.

    • The center of the neural plate sinks inwards, creating the neural groove. The sides rise upwards forming the neural folds.

    • Neurulation is the process of turning the neural plate into the neural tube, which will eventually become the brain and spinal chord.

    • The neural tube then closes and separates from the ectoderm. The surface ectoderm will eventually contribute to the epidermis of the skin.

    • The neural folds begin fusing during the third week, but for a period of time the ends remain open. These are called neuropores.

    • Cranial neuropore: head end

    • Caudal neuropore: tail end

    • Clinically important because failure of the neural tube to close causes neural tube defects, like spina bifida.

  • Neural crest cells

    • While the neural folds are coming together, some cells along the edges break away. These are called neural crest cells, which undergo epithelial-to-mesenchymal transition (EMT).

    • Neural crest cells migrate throughout the embryo and differentiate into many different structures, like the dorsal root (spinal) ganglia, autonomic ganglia, parts of cranial nerve ganglia, and Schwann cells.

    • The neural crest contributes to the pia mater, arachnoid mater, melanocytes, the adrenal medulla, and extensively to the development of the face and skull.

    • The mesoderm becomes the dura mater.

  • Distinctions

    • Neural plate: flat thickened nueroectoderm, is precursor to neural tube

    • Neural groove: dip down the middle, helps plate fold

    • Neural folds: raised edges, move together and fuse

    • Neural tube: closed tube, makes CNS

    • Neural crest: cells that break away from edges, are migratory cells that form many structures in the PNS

    • Surface ectoderm: ectoderm that closes over the neural tube, becomes epidermis.

  • Paraxial mesoderm is closest to the notochord/neural tube.

    • These columns of mesoderm start breaking into little paired blocks called somites. They form from cranial to caudal.

    • Somites contribute to the axial skeleton (vertebral column and ribs), skeletal muscle, and dermis of the back/body wall.

  • Farther away from the notochord is the lateral plate mesoderm.

    • Tiny spaced begin appearing inside the lateral plate mesoderm, forming the intraembryonic coelom. Major precursor of our major body cavities.

    • The lateral plate mesoderm gets divided into the somatic/parietal mesoderm (closer to the ectoderm, towards body wall), and the splanchnic/visceral mesoderm (closer to the endoderm, towards gut).

    • The intraembryonic coelom gets partitioned into the pericardial cavity and pleural cavity.

  • The embryo needs oxygen and nutrients, so the cardiovascular system is the first organ system to become functional.

  • There are two ways to make blood vessels:

    • Vasculogenesis: mesenchymal cells differentiate into angioblasts (vascular precursor cells), which group together and build new blood vessels.

    • Angiogenesis: new blood vessels grow out from the existing blood vessels.

  • Blood formation begins

    • Early blood cells develop in association with the umbilical vesicle and allantois.

  • Meanwhile, the heart is developing.

    • Mesoderm migrated cranially and formed the cardiogenic mesoderm. There are two endocardial heart tubes.

    • The tubes fuse and form the primordial heart tube.

    • The heart starts beating around day 21-22

  • Placenta

    • Chorionic villi are finger-like projections associated with the developing placenta.

    • The primary villus is trophoblast layers, and mesenchyme grows into the center.

    • The secondary villus has a mesenchymal chore, where blood vessels develop.

    • The tertiary villus now has fetal capillaries and blood vessels.

    • Maternal blood and fetal blood normally do not directly mix. Instead, substances cross the placental barrier.

    • Stem/anchoring villi help anchor the chorionic sac to maternal tissue, and branch villi are the major sites of maternal and fetal exchange.

Chapter 5

  • Embryonic folding: At the beginning of week 4, the embryo is still a flat trilaminar disc.

    • Head folding: at the cranial end, the rapidly growing brain causes the embryo to fold forward. The heart and oropharyngeal membrane move onto the ventral surface, and part of the yolk sac gets incorporated into the embryo as the foregut.

    • The foregut will contribute to the pharynx, esophagus, and lower respiratory systems.

    • The septum transversum moves into a position caudal to the heart and later contributes to the central tendon of the diaphragm.

    • Tail folding: the growth of the developing spinal cord causes a tail fold, and part of the yolk sac endoderm becomes incorporated into the embryo as the hindgut contributes to the colon and rectum.

    • Its terminal region enlarges into the cloaca, which develops into the urinary bladder and rectal region.

    • Side to side folding: The embryo folds inward from its right and left sides, and fuse along the ventral midline. This turns the flat disc into a cylinder. Another part of the yolk sac endoderm gets brought inside as the midgut, that forms the small intestine.

    • The midgut’s connection with the remaining yolk sac becomes narrower and forms the omphaloenteric duct.

  • Ectoderm: outside and nervous system

    • Forms the CNS, PNS, sensory structures, epidermis, hair, nails, mammary glands, tooth enamel, and parts of the pituitary.

  • Mesoderm: muscle, bone, blood, kidneys, reproductive system

    • Contributes to connective tissue, cartilage, bone, skeletal and smooth muscle, heart, blood, and lymphatic vessels, kidneys, ovaries, testes, spleen, serous membranes, and adrenal cortex.

  • Ectoderm: inner epithelial linings and digestive/respiratory organs

    • Forms much of the epithelial lining of the digestive and respiratory systems, and contributes to the liver, pancreas, thyroid, parathyroids, thymus, bladder lining, and much of the urethral lining.

  • Embryonic deleveopment

    • Induction (the process where one tissue influences how another tissue develops) is controlled by a combination of genes and interactions between nearby cells and tissues.

    • Signals between tissues can happen through signaling molecules such as Sonic hedgehog (Shh), extracellular matrix interactions, or direct cell to cell contact.

  • Week 4: major body remodeling

    • The neural tube closure is continuing, and heart is pumping, and the pharyngeal arches become visual.

    • Around days 26-27, the upper limb buds appear, the cranial neuropore has closed, early internal ear structures are visible, and early eye structures appear.

    • By day 28, both upper and lower limb buds are present, both neuropores have closed, and the embryo has a pronounced C shape.

  • Week 5: the head grows rapidly

    • Less dramatic change in overall body shape

    • The head grows much faster than the rest of the embryo.

  • Week 6: limbs, fingers, ears, and movement

    • The embryo begins making spontaneous movements.

    • The upper limbs become more recognizable: elbows begin forming, hand plates develop, and digital rays appear (early outlines of fingers)

    • Auricular hillocks begin forming around the ear region and contribute to external ear

    • The eyes become more obvious as retinal pigment develops.

    • Physiological umbilical herniation occurs, where the growing intestine temporarily extends into the proximal umbilical cord because the abdominal cavity is still too small.

  • Week 7: fingers and toes become more obvious

    • Limbs undergo major changes

    • Notches develop between digital rays

    • Ossification starts beginning in parts of skeleton.

  • Week 8: much more human looking

    • Final week of embryonic period

    • Fingers are separated, but still webbed

    • Limbs are recognizable and limb movement begins

    • Ossification begins in the femur

    • Embryonic tail has disappeared and neck is established.

    • 8 weeks gestational age is about 6 weeks after fertilization.