UNSW Embryology
The Developing Human: Clinically Oriented Embryology
Citation: The Developing Human: Clinically Oriented Embryology 8th ed. Moore, Keith L; Persaud, T V N; Torchia, Mark G Philadelphia, PA : Saunders/Elsevier, c2011. (links only function with UNSW connection)
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BGDA Practical Classes
First 8 Weeks
The Carnegie stages of the first 8 week of human development.
Week 3
Mesoderm means the "middle layer" and it is from this layer that the body's connective tissues are derived (note that the head neural crest ectoderm also forms connective tissues)
In early mesoderm development a number of transient structures will form and then be lost as tissue structure is patterned and organised.
Humans as vertebrates have a "backbone" and the first mesoderm structure we will see form after the notochord will be somites.
neural tube and neural crest
Mesoderm organization: (left to right)
lateral plate - intermediate mesoderm - paraxial mesoderm - axial mesoderm - paraxial mesoderm - intermediate mesoderm - lateral plate
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Stage 7 paraxial mesoderm
Stage 7 intermediate mesoderm
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Axial Mesoderm
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- Axial Mesoderm = notochord
- mechanical role in embryonic disc folding
- molecular role in patterning surrounding tissues
Adult - contributes to the nucleus pulposis of the intervertebral disc
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Stage 7 primitive-streak-node
Stage 7 cloacal-oral-membranes
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Paraxial Mesoderm
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- differentiates rostro-caudally (head to tail)
- head region - remains unsegmented
- body region - segments to form pairs of somites along the length of the embryo.
Adult - contributes vertebral column (vertebra and IVD), dermis of the skin, skeletal muscle of body and limbs
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Intermediate Mesoderm
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- named by position (between paraxial and lateral plate)
- differentiates rostro-caudally (head to tail)
- forms 3 sets of "kidneys" in sequence
- pronephros
- mesonephros
- metanephros
Adult - metanephros forms the kidney
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Lateral Plate Mesoderm
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- at edge of embryonic disc
- "horseshoe shaped" space forms in the middle, dividing this region
- somatic mesoderm - closest to ectoderm
- intra-embryonic coelom - single space forms the 3 major body cavities (pericardial, pleural, peritoneal)
- splanchnic mesoderm - closest to endoderm
Adult - body connective tissues, gastrointestinal tract (connective tissues, muscle, organs), heart
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Week 4
Somite Development
Somite initially forms 2 main components
- ventromedial- sclerotome forms vertebral body and intervertebral disc
- dorsolateral - dermomyotome forms dermis and skeletal muscle
sclerotome and dermomyotome
epaxial and hypaxial muscles
Sclerotome
- sclerotome later becomes subdivided
- rostral and caudal halves separated laterally by von Ebner's fissure
- half somites contribute to a single vertebral level body
- other half intervertebral disc
- therefore final vertebral segmentation “shifts”
Myotome
- Body - epaxial and hypaxial muscles
- Limbs - flexor and extensor muscles
Dermatome
- connective tissue underlying epidermis
- begins as a dorsal thickening
- spreads throughout the body
Heart
Mesoderm vascular development
- forms initially in splanchnic mesoderm of prechordal plate region - cardiogenic region
- growth and folding of the embryo moves heart ventrallly and downward into anatomical position
- week 3 begins as paired heart tubes that fuse to form single heart tube
- begins to beat in Humans- day 22-23
- heart tube connects to blood vessels forming in splanchnic and extraembryonic mesoderm
Week 2-3 pair of thin -walled tubes
Week 3 tubes fused, truncus arteriosus outflow, heart contracting
Week 4 heart tube continues to elongate, curving to form S shape
Week 5 Septation starts, atrial and ventricular
Septation continues, atrial septa remains open, foramen ovale
- Links: Cardiac Embryology
Neural
Stage 10 Week 4, 22 - 23 days
Stage 11 neural groove to tube
Neural Plate
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- extends from buccopharyngeal membrane to primitive node
- forms above notochord and paraxial mesoderm
- neuroectodermal cells
- broad brain plate
- narrower spinal cord
- 3 components form: floor plate, neural plate, neural crest
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Neural Groove
- forms in the midline of the neural plate (day 18-19)
- either side of which are the neural folds which continues to deepen until about week 4
- neural folds begins to fuse, beginning at 4th somite level
Neural Tube
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- the neural tube forms the brain and spinal cord
- fusion of neural groove extends rostrally and caudally
- begins at the level of 4th somite
- closes neural groove "zips up" in some species.
- humans appear to close at multiple points along the tube.
- leaves 2 openings at either end - Neuropores
- cranial neuropore closes before caudal
Failure for the neural tube to close correctly or completely results in a neural tube defect.
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Neural - 3 primary vesicles
Neural Crest
- population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses
- dorsal to the neural tube, as a pair of streaks
- pluripotential, forms many different types of cells
- cells migrate throughout the embryo
Neural Crest Derivatives: dorsal root ganglia, autonomic ganglia, adrenal medulla, drg sheath cells, glia, pia-arachnoid sheath, skin melanocytes, connective tissue of cardiac outflow, thyroid parafollicular cells, craniofacial skeleton, teeth odontoblasts
Head
Stage 14 pharyngeal arches
- branchial arch (Gk. branchia= gill)
- arch consists of all 3 trilaminar embryo layers (ectoderm- outside, mesoderm - core of mesenchyme, endoderm - inside)
- Humans have 5 arches - 1, 2, 3, 4, 6 (Arch 5 does not form or regresses rapidly)
- from in rostro-caudal sequence, Arch 1 to 6 from week 4 onwards
- arch 1 and 2 appear at time of closure of cranial neuropore
- Face - mainly arch 1 and 2
- Neck components - arch 3 and 4 (arch 4 and 6 fuse)
Sensory Placodes
- During week 4 a series of thickened surface ectodermal patches form in pairs rostro-caudally in the head region.
- These sensory placodes will later contribute key components of each of our special senses (vision, hearing and smell).
- Note that their initial postion on the developing head is significantly different to their final position in the future sensory system
- Otic placode - istage 13/14 embryo the otic placode sunk from the surface ectoderm to form a hollow epithelial ball, the otocyst, which now lies beneath the surface surrounded by mesenchyme (mesoderm). The epithelia of this ball varies in thickness and has begun to distort, it will eventually form the inner ear membranous labyrinth.
- Lens placode - lies on the surface, adjacent to the outpocketing of the nervous system (which will for the retina) and will form the lens.
- Nasal placode - has 2 components (medial and lateral) and will form the nose olefactory epithelium.
Upper and Lower Limb
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- Limb development occurs at different times for forelimbs and hindlimbs.
- mid-4th week human upper limb buds first
- lower limbs about 2 days later
- The limbs form at vertebra segmental levels C5-C8 (upper limbs) L3-L5 (lower limbs).
- Limbs are initially undifferentiated mesenchyme (mesoderm) with an epithelial (ectoderm) covering.
- Blood vessels then begin forming, the largest (marginal vein) is adjacent to tip of the bud.
- Myotome invade the bud.
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Gastrointestinal Tract
- Begins at buccopharyngeal membrane
- Ends at cloacal membrane
- 3 distinct portions (fore-, mid- and hind-gut)
- liver earliest forming organ
Germ layer contributions
- Endoderm - epithelium and associated glands
- Mesoderm (splanchnic) - mesentry, connective tissues, smooth muscle, blood vessels
- Ectoderm (neural crest) - enteric nervous system
Both endoderm and mesoderm will contribute to associated organs.
Week 5
Stage 14 pharyngeal arches
Neural - 5 secondary vesicles
- Heart - septation starts, atrial and ventricular
- Vascular - 3 vascular systems (systemic, placental, vitelline) extensively remodelled
- Respiratory - left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)
- Sense - Hearing cochlear part of otic vesicle elongates (humans 2.5 turns)
Week 6
- Endocrine development
- Pituitary - connecting stalk between pouch and oral cavity degenerates
- Parathyroid - diverticulum elongate, hollow then solid, dorsal cell proliferation
- Thymus - diverticulum elongate, hollow then solid, ventral cell proliferation
- Adrenal - fetal cortex forms from mesothelium adjacent to dorsal mesentery, medulla neural crest cells from adjacent sympathetic ganglia
Week 7
- Pancreas - Week 7 to 20 pancreatic hormones secretion increases, small amount maternal insulin
- Limb bones form by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5 onward).
Endochondral ossification in limb
Endochondral ossification
Head Intramembranous ossification
Intramembranous ossification
Week 8
Neural - secondary vesicles
Neural - early developing cortex
Gastrointestinal tract herniation
- Limb upper and lower limbs rotate in different directions (upper limb dorsally, lower limb ventrally)
Links: Embryonic Development | Timeline human development
Fetal
Fetal length and weight changes
- First Trimester (1 - 12 weeks) - embryonic and early fetal
- Second Trimester (13 - 24 weeks) - organ development and function, growth (length)
- Third Trimester (25 - 40 weeks) - organ function and rapid growth (weight)
Fetal Neural
Timeline of events in Human Neural Development
- During the fetal period there is ongoing growth in size, weight and surface area of the brain and spinal cord. Microscopically there is ongoing: cell migration, extension of processes, cell death and glial cell development.
- Brain - folding of the initially smooth surface (Insular cortex, Gyral and Sulcal development)
- Neural development will continue after birth with substantial growth, death and reorganization occuring during the postnatal period
Lung Stages
- week 4 - 5 embryonic
- week 5 - 17 pseudoglandular
- week 16 - 25 canalicular
- week 24 - 40 terminal sac
- late fetal - 8 years alveolar
Fetal Genital
- ovary and testis development
- external genital development
- testis descent
Fetal Renal
- week 32-34 nephron development completed
- term birth nephron number per kidney about 1 million (300,000 to 2 million)
Fetal Endocrine
- Many endocrine organs begin to function in the early fetal period.
- Pituitary Hormones - HPA axis established by week 20, pituitary functional throughout fetal development
- Thyroid Hormone - important for neural development, required for metabolic activity, also in the newborn
Remember that the Placenta also has important endocrine functions during development.
Critical Periods
The term "Critical Periods" refers to periods of development when specific systems are more sensitive to teratogen exposure or developmental insults.
Conceptus
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Embryonic development (weeks)
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Fetal period (weeks)
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1
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2
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3
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4
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5
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6
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7
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8
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9
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16
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20-36
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38
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Neural
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Heart
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Upper limbs
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Lower limbs
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Ear
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Eye
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Palate
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Teeth
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External genitalia
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Loss
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Major abnormalities
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Functional and Minor abnormalities
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Next
Carnegie Stage Table
Weeks shown in the table below are embryonic post ovulation age, for clinical Gestational Age (GA) measured from last menstrual period, add 2 weeks.
Stage
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Days (approx)
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Size (mm)
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Images (not to scale)
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Events
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1
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1 (week 1)
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0.1 - 0.15
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fertilized oocyte, zygote, pronuclei
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2
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2 - 3
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0.1 - 0.2
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morula cell division with reduction in cytoplasmic volume, blastocyst formation of inner and outer cell mass
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3
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4 - 5
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0.1 - 0.2
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loss of zona pellucida, free blastocyst
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4
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5 - 6
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0.1 - 0.2
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attaching blastocyst
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5
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7 - 12 (week 2)
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0.1 - 0.2
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implantation
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6
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13 - 15
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0.2
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extraembryonic mesoderm, primitive streak, gastrulation
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7
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15 - 17 (week 3)
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0.4
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gastrulation, notochordal process
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8
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17 - 19
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1.0 - 1.5
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primitive pit, notochordal canal
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9
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19 - 21
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1.5 - 2.5
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Somitogenesis Somite Number 1 - 3 neural folds, cardiac primordium, head fold
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10
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22 - 23 (week 4)
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2 - 3.5
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Somite Number 4 - 12 neural fold fuses
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11
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23 - 26
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2.5 - 4.5
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Somite Number 13 - 20 rostral neuropore closes
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12
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26 - 30
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3 - 5
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Somite Number 21 - 29 caudal neuropore closes
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13
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28 - 32 (week 5)
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4 - 6
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Somite Number 30 leg buds, lens placode, pharyngeal arches
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Stage 13/14 shown in serial embryo sections series of Embryology Program
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14
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31 - 35
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5 - 7
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lens pit, optic cup
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15
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35 - 38
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7 - 9
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lens vesicle, nasal pit, hand plate
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16
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37 - 42 (week 6)
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8 - 11
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nasal pits moved ventrally, auricular hillocks, foot plate
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17
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42 - 44
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11 - 14
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finger rays
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18
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44 - 48 (week 7)
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13 - 17
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ossification commences
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19
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48 - 51
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16 - 18
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straightening of trunk
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20
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51 - 53 (week 8)
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18 - 22
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upper limbs longer and bent at elbow
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21
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53 - 54
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22 - 24
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hands and feet turned inward
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Stage 22 shown in serial embryo sections series of Embryology Program
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22
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54 - 56
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23 - 28
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eyelids, external ears
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23
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56 - 60
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27 - 31
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rounded head, body and limbs
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Following this stage Fetal Development occurs until birth (approx 37 weeks)
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The embryos shown in the table are from the Kyoto and Carnegie collection and other sources.
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Cite this page: Hill, M.A. (2024, April 24) Embryology BGDA Lecture - Development of the Embryo/Fetus 2. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/BGDA_Lecture_-_Development_of_the_Embryo/Fetus_2
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- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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