Embryonic Period & Carnegie Stages

• Development during the Embryonic Period occurs up to ~8 weeks

Carnegie Stages of Human Development

• Stage 1: Zygote appears around day 1
• Stage 2: Occurs around day 3
• Stage 3: Occurs around day 4
• Stage 7: Occurs between days 15-17
• Stage 8: Occurs between days 17-19
• Stage 9: Occurs between days 19-21
• Stage 10: Occurs between days 21-23
• Stage 11: Occurs between days 23-26
• Stage 12: Occurs between days 26-30
• Stage 13: Occurs between days 28-32
• Stage 14: Occurs between days 31-35
• Stage 15: Occurs between days 35-38
• Stage 16: Occurs between days 37-42
• Stage 17: Occurs between days 42-44
• Stage 18: Occurs between days 44-48
• Stage 19: Occurs between days 48-51
• Stage 20: Occurs between days 51-53
• Stage 21: Occurs between days 53-54
• Stage 22: Occurs between days 54-58
• Stage 23: Occurs between days 56-60

Gastrulation

• Gastrulation establishes the three definitive germ layers of the embryo
• The germ layers are called the ectoderm, intraembryonic mesoderm, and endoderm
• Gastrulation forms a trilaminar embryonic disk
• The three germ layers produce all tissues and organs of the adult

Week 8

• By the end of week 8, the embryo has a distinct human appearance
• All major organ systems begin development but have minimal functionality
• The uteroplacental circulation cannot satisfy the embryo's increasing nutritional needs
• The development of the cardiovascular system is essential at this stage

Neurulation

• Neurulation involves the formation of the neural plate and neural folds
• The neural folds close to form the neural tube
• These processes are completed by the end of the fourth week
• Closure of the caudal neuropore occurs at the end of the fourth week

Neural Plate and Neural Tube

• The notochord induces the overlying embryonic ectoderm to thicken
• This forms an elongated neural plate of thickened neuroepithelial cells
• The ectoderm of the neural plate/neuroectoderm gives rise to the central nervous system (CNS)
• The brain and spinal cord, and other structures, arise from the ectoderm of the neural plate
• The neural plate appears cranial to the primitive node and dorsal to the notochord
• The neural plate broadens and extends cranially as the notochord elongates
• On ~day 18, the neural plate invaginates along its central axis
• The invagination forms a median neural groove with neural folds on each side
• The neural folds are the first signs of brain development
• By the end of the third week, the neural folds move together and fuse
• The neural folds convert the neural plate into the neural tube, the primordium of the brain vesicles and spinal cord
• The lateral edges of the neural folds first begin to fuse on day 22
• The neural tube soon separates from the surface ectoderm as the neural folds meet
• The free edges of the ectoderm fuse, making this layer continuous over the neural tube
• The surface ectoderm differentiates into the epidermis of the skin
• Neurulation is completed during the fourth week
• The fusion of the neural folds results in the formation of the neural tube
• The neural tube is open at both the anterior and posterior neuropores
• The fusion of the neural folds advances both cranially and caudally
• The failure of the neuropores to close results in lower neural tube defects
• Examples of neural tube defects include anencephaly and spina bifida
• The neural tube lengthens as it zips up both cranially and caudally
• The anterior neuropore closes at day 24-25 and becomes the lamina terminalis
• The posterior neuropore closes at day 26-27

Derivatives of the neural tube

• Neurons of the CNS
• Glia (supporting cells) of the CNS
• Somatomotor neurons of the PNS
• Presynaptic autonomic neurons of PNS
• The ventricular system of the brain and central canal of the spinal cord (the lumen of the neural tube)

Derivatives of the neural crest

• Sensory neurons in the PNS
• Postsynaptic autonomic neurons
• Schwann cells
• Arachnoid and pia mater of meninges (Note dura mater is from mesoderm)
• Adrenal medulla cells
• Head mesenchyme
• Melanocytes in the skin

Neural Crest Formation

• As the neural folds fuse to form the neural tube, some neuroectodermal cells lose their epithelial affinities
• These cells lie along the crest of each neural fold
• They also lose attachments to neighboring cells
• As the neural tube separates from the surface ectoderm, these neural crest cells migrate dorsolaterally
• This migration occurs on each side of the neural tube
• They form the neural crest between the neural tube and the overlying surface ectoderm
• The neural crest soon separates into right and left parts
• These parts migrate to the dorsolateral aspects of the neural tube
• Neural crest cells differentiate into various cell types

Neural crest cell types include

• Spinal ganglia and the ganglia of the autonomic nervous system
• Ganglia of cranial nerves V, VII, IX, and X (partially)
• Sheaths of the peripheral nerves
• The pia mater and arachnoid mater

Embryo Folding

• Embryo Folding happens during the 4th week
• During the embryonic period, craniocaudal and lateral folding occur
• These folding changes change the shape of the embryo from a two-dimensional disk to a three-dimensional cylinder
• The developing embryo folds into a tubular structure

Additional folding info

• The embryo is attached to the yolk sac on the ventral side
• The dorsal axis is stiff due to the developing notochord, neural tube, and somites
• The cranial fold, caudal fold, and lateral folds form
• Lateral folds grow and enclose the body into a tubular structure

Mesoderm

• The intraembryonic mesoderm proliferates on each side to form a thick, longitudinal column of paraxial mesoderm
• As the notochord and neural tube form
• Each column is continuous laterally with the intermediate mesoderm
• The intermediate mesoderm gradually thins into a layer of lateral mesoderm
• The lateral mesoderm is continuous with the extraembryonic mesoderm
• The extraembryonic mesoderm covers the umbilical vesicle and amnion
• The paraxial mesoderm differentiates at the end of the third week
• It divides into paired cuboidal bodies, or somites, on each side of the developing neural tube

Somites

• The somites form distinct surface elevations on the embryo
• The somites appear somewhat triangular on transverse section
• The first pair of somites appears at the end of the third week near the cranial end of the notochord
• Subsequent pairs form in a craniocaudal sequence
• The somites are prominent during the fourth and fifth weeks
• Somites are used as one of several criteria for determining an embryo's age

Somites give rise to

• Most of the axial skeleton and the associated musculature
• The adjacent dermis of the skin

Coelom

• The intraembryonic coelom first appears as small, isolated, coelomic spaces
• This occurs in the lateral mesoderm and cardiogenic mesoderm

Additional coelom info

• Coelomic spaces coalesce to form a single, horseshoe-shaped intraembryonic coelom
• The coelom divides the lateral mesoderm into two layers
• The layers are somatopleuric mesoderm and splanchnopleuric mesoderm
• The serosal membranes line the coelom
• Somatopleuric (a somatic, or parietal) mesoderm, is continuous with the extraembryonic mesoderm
• The extraembryonic mesoderm covers the amnion
• Somatopleuric mesoderm forms the somatopleure with the embryonic ectoderm
• The somatopleure is the embryonic body wall
• Splanchnopleuric (splanchnic or visceral) mesoderm is continuous with the extraembryonic mesoderm
• The extraembryonic mesoderm covers the umbilical vesicle
• The splanchnopleuric mesoderm forms the splanchnopleure with the embryonic endoderm
• The splanchnopleure is the wall of the gut

Embryonic Nutrition and Cardiovascular System

• At the end of the 2nd week, embryonic nutrition is obtained from the maternal blood
• Nutrition is obtained via diffusion through the extraembryonic coelom and yolk sac (umbilical vesicle)
• The early formation of the cardiovascular system correlates with the transportation of oxygen and nourishment
• The transportation of oxygen and nourishment occurs through the maternal circulation through the chorion
• At the beginning of the 3rd week, the formation of blood and blood vessels begins
• This process occurs in the mesodermal wall of the yolk sac and in the wall of the chorion outside the embryo proper
• Stimulated by an inductive interaction with the endoderm of the yolk sac
• Many hemangioblastic aggregates (blood islands), consisting of stem cells called hemangioblasts, appear
• They appear in the extraembryonic splanchnic mesoderm of the yolk sac
• The heart and great vessels form from mesenchymal cells in the heart primordium (cardiogenic area)
• The heart is carried from its initial cranial location towards the middle of the embryo by folding
• Paired, endothelium-lined channels-endocardial heart tubes-develop
• These form during the third week and fuse to form a primordial heart tube
• The tubular heart joins with blood vessels in the embryo, connecting stalk, chorion, and umbilical vesicle
• The heart forms a primordial cardiovascular system
• By the end of the third week, blood is flowing and the heart begins to beat on day 21 or 22
• The cardiovascular system is the first major system to function in the embryo

The Fourth Week

• At the beginning of the 4th week, the embryonic disc is flat and trilaminar
• Body folding commences during the fourth week
• Body folding is complete, yielding a three-dimensional embryo
• The body plan has a tube-within-a-tube structure with an intraembryonic coelom
• It also has an amniotic sac
• At the end of the 3rd week, the embryo is a flat, ovoid, trilaminar disc
• During the 4th week, embryonic folding converts the embryo into a 3D structure
• The embryonic folding represents the vertebrate body plan
• The main force responsible for folding is the differential growth of structures
• The embryonic disc and amnion grow rapidly
• The yolk sac does not grow rapidly
• Major changes in body form occur during the fourth week
• At the beginning, the embryo is almost straight

Additional notes on fourth week

• The somites produce surface elevations
• The neural tube is open at the rostral and caudal neuropores
• By 24 days, the pharyngeal arches have appeared
• The embryo is now slightly curved because of the head and tail folds
• The early heart produces a large ventral prominence and pumps blood
• The rostral neuropore is closing at 24 days
• At 26 days, the forebrain produces a prominent elevation of the head
• The long, curved caudal eminence (tail-like structure) is present
• At 28 days, upper limb buds are recognizable as small swellings on the ventrolateral body walls
• At 26 days, the otic pits (primordia of internal ears) are also visible
• Ectodermal thickenings, the lens placodes, are also visible

Fourth Week Continued

• The fourth pair of pharyngeal arches and the lower limb buds are visible by the end of the fourth week
• By the end of the fourth week, the caudal neuropore is usually closed
• Rudiments of many organ systems, especially the cardiovascular system, are established

Fifth & Sixth Weeks

• Changes in body form are minor during the fifth week
• Growth of the head exceeds that of other regions
• This is caused mainly by the rapid development of the brain and facial prominences
• The face soon contacts the heart prominence
• The mesonephric ridges indicate the site of the mesonephric kidneys
• Embryos in the sixth week show spontaneous movements, such as twitching of the trunk and limbs
• Embryos at this stage show reflex responses to touch
• The primordia of the digits (fingers) —the digital rays-begin to develop in the hand plates
• Several small auricle hillocks, develop and contribute to the formation of the External ear
• The eyes are now obvious largely because retinal pigment has formed
• The head is much larger relative to the trunk
• The head is bent over the large heart prominence
• The trunk then begins to straighten
• The intestines enter the extraembryonic coelom in the proximal part of the umbilical cord: umbilical herniation

Seventh & Eighth Weeks

• The limbs undergo considerable change during the seventh week
• Notches appear between the digital rays in the hand plates, partially separating the future digits
• At the beginning of the eighth -final- week of the embryonic period, the digits of the hand are separated, but noticeably webbed
• At the end of the fetal period, the digits have lengthened and are separated
• Coordinated limb movements first occur during this week
• All evidence of the tail-like caudal eminence has disappeared by the end of the eighth week
• The head is still disproportionately large, constituting almost half of the embryo
• The neck region is established and the eyelids are closing
• The auricles of the external ears begin to assume their final shape, but are still low-set on the head