BGDA Lecture - Development of the Embryo/Fetus 2

Embryology - 11 Dec 2023 Expand to Translate
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Introduction

This lecture covers the period of Embryonic development, in Humans from week 3 to week 8 (GA week 5-10) and is divided into 23 Carnegie stages of embryonic development. There will also be a brief introduction to fetal development. Note, the period from week 9 to week 38 is considered Fetal development and will be covered in detail in the Laboratory 12.

2019 Lecture PDF

Lecture Objectives

Understand key structures and events in embryonic development.
Understanding of the dynamic changes internal and external structures.
Brief understanding of organ and system formation (functional / not functional).
Brief understanding of critical periods of development.

1 Minute Embryology | UNSW theBox

Lecture Archive
[Media:2018 BGDA Lecture - Development of the Embryo-Fetus 2.pdf 2018 PDF] \| 2017 \| 2017 PDF \| 2016 \| 2015 \| 2014 \| 2014 PDF \| 2013 \| 2012 \| 2010 \| Practical 6 Embryonic Development \| Practical 12 Fetal Development

Textbooks

UNSW Embryology

Hill, M.A. (2020). UNSW Embryology (20th ed.) Retrieved December 11, 2023, from https://embryology.med.unsw.edu.au

human timeline | first trimester timeline
Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8
fetal
abnormal development | birth | neonatal | Neonatal Diagnosis

The Developing Human: Clinically Oriented Embryology

Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders. (links only function with UNSW connection)

Chapter 5 Fourth to Eighth Weeks of Human Development

Chapter 6 Fetal Period

Chapter 20 Human Birth Defects

The Developing Human: Clinically Oriented Embryology (10th edn)
UNSW Students have online access to the current 10th edn. through the UNSW Library subscription (with student Zpass log-in). APA Citation: Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders. Links: PermaLink \| UNSW Embryology Textbooks \| Embryology Textbooks \| UNSW Library
Introduction to the Developing Human First Week of Human Development Second Week of Human Development Third Week of Human Development Fourth to Eighth Weeks of Human Development Fetal Period Placenta and Fetal Membranes Body Cavities and Diaphragm Pharyngeal Apparatus, Face, and Neck Respiratory System Alimentary System Urogenital System Cardiovascular System Skeletal System Muscular System Development of Limbs Nervous System Development of Eyes and Ears Integumentary System Human Birth Defects Common Signaling Pathways Used During Development Appendix : Discussion of Clinically Oriented Problems

Larsen's Human Embryology

Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.(links only function with UNSW connection)

Chapter 4 Fourth Week: Forming the Embryo

Chapter 6 Fetal Development and the Fetus as Patient

Larsen's Human Embryology (5th edn)
UNSW students have full access to this textbook edition through UNSW Library subscription (with student Zpass log-in). APA Citation: Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone. Links: PermaLink \| UNSW Embryology Textbooks \| Embryology Textbooks \| UNSW Library
Gametogenesis, Fertilization, and First Week Second Week: Becoming Bilaminar and Fully Implanting Third Week: Becoming Trilaminar and Establishing Body Axes Fourth Week: Forming the Embryo Principles and Mechanisms of Morphogenesis and Dysmorphogenesis Fetal Development and the Fetus as Patient Development of the Skin and Its Derivatives Development of the Musculoskeletal System Development of the Central Nervous System Development of the Peripheral Nervous System Development of the Respiratory System and Body Cavities Development of the Heart Development of the Vasculature Development of the Gastrointestinal Tract Development of the Urinary System Development of the Reproductive System Development of the Pharyngeal Apparatus and Face Development of the Ears Development of the Eyes Development of the Limbs

More Textbooks?

BGDA Practical Classes

Practical 3 - Fertilization to Implantation	Practical 6 - Implantation to 8 Weeks	Practical 12 - Fetal Period
	Practical 14 - Placenta and Fetal Membranes

First 8 Weeks

The Carnegie stages of the first 8 week of human development.

Week 3

Week 3 - Gastrulation

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.

Mesoderm and Ectoderm Cartoons
Trilaminar Embryo
Paraxial and Lateral Plate
somites
Somatic and Splanchnic

Mesoderm organization: (left to right)

lateral plate - intermediate mesoderm - paraxial mesoderm - axial mesoderm - paraxial mesoderm - intermediate mesoderm - lateral plate

axial mesoderm
Stage 7 paraxial mesoderm
Stage 7 intermediate mesoderm
Stage 7 lateral plate

Axial Mesoderm

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

Stage 7 primitive-streak-node
Stage 7 cloacal-oral-membranes

Paraxial Mesoderm

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

Intermediate Mesoderm

named by position (between paraxial and lateral plate)
differentiates rostro-caudally (head to tail)
renal forms 3 sets of "kidneys" in sequence

pronephros
mesonephros
metanephros

Adult - metanephros forms the renal kidney

Lateral Plate Mesoderm

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

Week 4

Somite Development

Stage 10 (early)
Stage 10 (late)
Stage 10 (labeled)
Stage 11
Stage 11

Somite initially forms 2 main components

ventromedial- sclerotome forms vertebral body and intervertebral disc
dorsolateral - dermomyotome forms dermis and skeletal muscle

paraxial mesoderm
early somite
sclerotome and dermomyotome
dermatome and myotome
epaxial and hypaxial muscles

Sclerotome	Dermatome
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”	connective tissue underlying epidermis begins as a dorsal thickening spreads throughout the body
	Myotome
	Body - epaxial and hypaxial muscles Limbs - flexor and extensor muscles

Heart

Heart Development Movies

‎‎Week 3

Page | Play

‎‎Heart Looping

Page | Play

‎‎Heart Realign

Page | Play

‎‎Atrial Septation

Page | Play

‎‎Outflow Septation

Page | Play

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

Links: Cardiac Embryology

Neural

Mesoderm and Ectoderm Cartoons
Trilaminar Embryo
Paraxial and Lateral Plate
somites
Somatic and Splanchnic

Stage 10 Week 4, 22 - 23 days

Stage 11 neural groove to tube

Neural Plate

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

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

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.

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

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.

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.

Gastrointestinal Tract

Week 5

Stage 14 pharyngeal arches

Stage 14
Stage 15
Respiratory Tract
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)

Atrial septa remains open, foramen ovale, septation continues (week 5-7),

<html5media height="720" width="560">File:Heart septation 003.mp4</html5media>

Week 6

Week 6 Face Development

Stage 16
Stage 17

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

Human week 7

Stage 18
Stage 19

pancreas - Week 7 to 20 pancreatic hormones secretion begins and increases, small amount maternal insulin
limb bones form by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5 onward; bone timeline)

Endochondral ossification in limb
Endochondral ossification
Head Intramembranous ossification
Intramembranous ossification

Week 8

Neural - secondary vesicles
Neural - early developing cortex
Gastrointestinal tract herniation

‎‎Sagittal GIT

Page | Play

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

Note - Fetal development topic will be covered in detail in practical 12 - Fetal. Information below is only a brief summary and may not be covered in this lecture.

First Trimester (1 - 12 weeks) - embryonic and early fetal
Second Trimester (13 - 24 weeks) - organ development, function, and 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 culcal development)
Neural development will continue after birth with substantial growth, death and reorganization occuring during the postnatal period

Links: neural | BGDA Lecture - Nervous System

Lung Stages

respiratory

week 4 - 5 embryonic
week 5 - 17 pseudoglandular
week 16 - 25 canalicular
week 24 - 40 terminal sac
late fetal - 8 years alveolar

Lung Stages (detailed)

**Human Lung Stages**
Lung Stage	Human	Features	Vascular
Embryonic	week 4 to 5	lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs	extra pulmonary artery then lobular artery
Pseudoglandular	week 5 to 17	conducting epithelial tubes surrounded by thick mesenchyme are formed, extensive airway branching	Pre-acinar arteries
Canalicular	week 16 to 25	bronchioles are produced, increasing number of capillaries in close contact with cuboidal epithelium and the beginning of alveolar epithelium development	Intra-acinar arteries
Saccular	week 24 to 40	alveolar ducts and air sacs are developed	alveolar duct arteries
Alveolar	late fetal to 8 years	secondary septation occurs, marked increase of the number and size of capillaries and alveoli	alveolar capillaries
embryonic stage - pseudoglandular stage - canalicular stage - saccular stage - alveolar stage Links: Species Stage Comparison \| respiratory

Links: respiratory | SH Lecture - Respiratory

Fetal Genital

genital

Gonad - ovary and testis development
Internal genital tract - uterus and ductus deferens
External genital tract - genital folds development
Testis descent

Links: genital | BGDB Lecture - Genital

Fetal Renal

renal

week 32-34 nephron development completed
term birth nephron number per kidney about 1 million (300,000 to 2 million)

Links: renal

Fetal Endocrine

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.

Links: endocrine | placenta

Critical Periods

The term "Critical Periods" refers to periods of development when specific systems are more sensitive to teratogen exposure or developmental insults.

Critical Periods of Human Development

Conceptus

Embryonic development (weeks)

Fetal period (weeks)

1

2

3

4

5

6

7

8

9

16

20-36

38

Neural

Heart

Upper limbs

Lower limbs

Ear

Eye

Palate

Teeth

External genitalia

Loss

Major abnormalities

Functional and Minor abnormalities

Additional Information

See the associated BGDA Practical 6 class.

Historic Embryology
1915 Congenital Cardiac Disease \| 1917 Frequency of Anomalies in Human Embryos \| 1920 Hydatiform Degeneration Tubal Pregnancy \| 1921 Anencephalic Embryo \| 1921 Rat and Man \| 1966 Congenital Malformations

First Trimester Timeline

Embryonic Weeks/Stages

Week:	1	2	3	4	5	6	7	8
Carnegie stage:	1 2 3 4	5 6	7 8 9	10 11 12 13	14 15	16 17	18 19	20 21 22 23

First Trimester Timeline

Links: human timeline | first trimester timeline | second trimester timeline | third trimester timeline

Gestational Day GA

Stage

Event

1

Menstrual Phase

menstrual cycle changes: uterus endometrium (loss), ovary (follicle development)

2

3

4

5

Proliferative Phase

menstrual cycle changes: uterus endometrium (proliferation), ovary (Follicle Development)

6

7

8

Proliferative Phase

9

menstrual cycle - Mid proliferative

10

11

12

13

menstrual cycle - Late Proliferative

14

ovulation

Capacitation

Fertilization Day

Stage

Event

1

Secretory Phase

Stage 1

fertilization, zygote, Secretory Phase

2

Stage 2

morula, Blastula

3

blastocyst

4

Stage 3

blastocyst Hatching (zona pellucida lost)

5

Late Secretory, blastocyst (free floating)

6

Stage 4

Adplantation

7

Stage 5

8

implantation

9

10

11

12

13

Stage 6

Chorionic Cavity

14

Day

Stage

Event

15

16

Stage 7

gastrulation, ectoderm, mesoderm, endoderm

17

18

Stage 8

neural neurogenesis, neural groove and folds are first seen

19

20

Stage 9

Musculoskeletal somitogenesis, first somites form and continue to be added in sequence caudally (1 - 3 somite pairs).

neural the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open

Neural Crest mesencephalic neural crest is visible^[1]

21

heart cardiogenesis, week 3 begins as paired heart tubes.

Day

Stage

Event

22

Stage 10

Neural Crest differentiation at spinal cord level from day 22 until day 26

neural folds begin to fuse near the junction between brain and spinal cord, when Neural Crest cells are arising mainly from the neural ectoderm

Neural Crest trigeminal, facial, and postotic ganglia components visible^[1]

Neural Crest migration of vagal level neural crest cells begins (7-10 somite stage)

neural rostral neural tube forms 3 primary brain vesicles (week 4)

respiratory Week 4 - laryngotracheal groove forms on floor foregut.

23

heart begins to beat in Humans by day 22-23, first functioning embryonic organ formed.

24

Stage 11

thyroid - thyroid median endodermal thickening in the floor of pharynx

neural rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in two areas simultaneously. The two lips, however, behave differently.

ventricular Optic ventricle appears and the neural groove/tube space is initially filled with amniotic fluid.^[2]

25

Stage 12

pituitary Week 4 hypophysial pouch, Rathke's pouch, diverticulum from roof

liver septum transversum forming liver stroma and hepatic diverticulum forming hepatic trabeculae^[3]

neural caudal neuropore takes a day to close (closure is approximately at future somitic pair 31/sacral vertebra 2)

neural secondary neurulation begins

ventricular onset of the ventricular system and separates the ependymal from the amniotic fluid.^[2]

neural crest cardiac crest, neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there the truncus arteriosus^[1]

neural crest vagal neural crest enter the foregut (20-25 somite stage)

26

27

28

Stage 13

neural the neural tube is normally completely closed, ventricular system now separated from amniotic fluid. Neural crest at spinal level is segregating, and spinal ganglia are in series with the somites. Spinal cord ventral roots beginning to develop.^[4]

telencephalon cavity appears

Neural - Vascular Development - hindbrain is supplied by two parallel neural arteries (or channels) that obtain their blood supply from carotid-vertebrobasilar anastomoses given by the pharyngeal arch arteries; trigeminal artery, the otic artery, hypoglossal artery, and the proatlantal artery.^[5]

liver epithelial cord proliferation enmeshing stromal capillaries^[3]

smell Crest comes from the nasal plates^[6]

integumentary 4 weeks - simple ectoderm epithelium over mesenchyme

integumentary 1-3 months ectoderm- germinative (basal) cell repeated division of generates stratified epithelium; mesoderm- differentiates into connective tissue and blood vessels

vision Optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lens placode.^[7]

Diaphragm - pleuroperitoneal fold (PPF) first discernible in human embryos (CRL 6mm).^[8]

29

pituitary Week 5 elongation, contacts infundibulum, diverticulum of diencephalon

heart Week 5 septation starts, atrial and ventricular

respiratory Week 5 left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)

Respiratory Week 5 to 17 lung histology - pseudoglandular

hearing Week 5 cochlear part of otic vesicle elongates (humans 2.5 turns)

30

31

32

Stage 14

Placodes sensory placodes, lens pit, otocyst, nasal placode, primary/secondary vesicles, fourth ventricle of brain

somite continued segmentation of paraxial mesoderm (somite pairs), heart prominence

head 1st, 2nd and 3rd pharyngeal arch, forebrain, site of lens placode, site of otic placode, stomodeum

Body - heart, liver, umbilical cord, mesonephric ridge visible externally as bulges.

limb upper and lower limb buds growing.

Abdominal Wall mesoderm of the primary body wall coalesced in the ventral midline to create the abdominal cavity.^[9]

neural first appearance of the future cerebral hemispheres. Cerebellar plate differentiated to an intermediate layer, and future rhombic lip identifiable^[10]

Neural - Vascular Development - basilar artery forms from the consolidation of the neural arteries.^[5]

ventricular Subarachnoid space initially as irregular spaces on the ventral surface of the spinal cord.^[11]

liver hepatic gland and its vascular channels enlarge, hematopoietic function appears^[3]

vision lens placode is indented by the lens pit.^[7]

33

Stage 15

neural cranial nerves (except olfactory and optic) are identifiable in more advanced embryos^[12]

Neural - Vascular Development - vertebral arteries form from transverse anastomoses between cervical intersegmental arteries, beginning with the proatlantal artery and proceeding downward to the 6th intersegmental artery,^[5]

vision lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.^[7]

34

35

vision 35 to 37 days retinal pigment present

36

pituitary Week 6 - connecting stalk between pouch and oral cavity degenerates

parathyroid Week 6 - diverticulum elongate, hollow then solid, dorsal cell proliferation

thymus Week 6 - diverticulum elongate, hollow then solid, ventral cell proliferation

adrenal Week 6 - fetal cortex forms from mesothelium adjacent to dorsal mesentery, medulla neural crest cells from adjacent sympathetic ganglia

respiratory Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes

tongue Week 6 - gustatory papilla, caudal midline near the foramen caecum (week 6 to 7 - nerve fibers approach the lingual epithelium)

37

Stage 16

Neural first parasympathetic ganglia, submandibular and ciliary, are identifiable^[13]

Neural - Vascular Development - development of the middle cerebral artery is first identified as small buds originating proximal to the anterior cerebral artery on the anterior division of the primitive internal carotid artery.^[5]

limb upper limb bud nerves median nerve, radial nerve and ulnar nerve entered into hand plate, myoblasts spindle shaped and oriented parallel to limb bud axis.

Abdominal Wall muscle cell migration about 25% of the hemicircumference of the abdominal cavity, the lateral plate mesoderm has become more condensed and thicker in the area around the myoblasts.^[9]

heart outflow tract elliptical configuration with four cushions, the two larger fusing at this stage. Semilunar valve leaflets form at the downstream end of the cushions

head lip and palate components of the upper lip, medial nasal prominence and maxillary process present, median palatine process appears.

Eyelid prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.^[7]

38

39

40

41

Stage 17

neural
- telencephalon areas of the future archicortex, paleocortex, and neocortex, visible. Beginning of future choroid plexus^[14]
- ventricular primordium of the epidural space appears first on the ventral part of the vertebral canal and develops rostro-caudally^[15]
smell olfactory nerve fibres enter the brain^[6]
Eyelid sulcus (groove) above and below eye deepen and eyelid folds develop (below first and then above)^[7]
Diaphragm - pleuroperitoneal fold (PPF) no longer separated from the diaphragm (CRL 14mm)^[8]
Abdominal Wall muscle cells now migrated approximately 50% of the distance to the ventral midline, inner and outer layers were not discernible yet.^[9]

42

heart separation of common cardiac outflow (aortic arch and pulmonary aorta)

Day

Stage

Event

43

pancreas Week 7 to 20 pancreatic hormones secretion increases, small amount maternal insulin

respiratory Week 7 - enlargement of liver stops descent of heart and lungs

44

Stage 18

limb bone forms by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5-12).

neural smell vomeronasal fibres and nervus terminalis^[6]

liverobturation due to epithelial proliferation, bile ducts became reorganized, continuity between liver cells and gut^[3]

ventricular duramater appears and spaces surround the circumference of the spinal cord, which coalesce and contain many blood vessels.^[15]

Female uterus opening of the paramesonephric (Müllerian) duct to the coelomic cavity formed as an invagination of the coelomic epithelium^[16]

Abdominal Wall separation of the myoblasts into distinct inner and outer layers, with unidirectional orientation. Abdominal wall thicker in the region where secondary structures were forming compared with the primary body wall region, dorsally outermost layer of connective tissue approximately half of this thickness.^[9]

45

liver (stage 18 to 23) biliary ductules developed in periportal connective tissue

produces ductal plates that receive biliary capillaries^[3]

46

47

48

Stage 19

vision - (stage 19 -22) eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.^[7]
cardiovascular
- arterial system^[17] Chapter 18 fig. 447).
- aortic arches ^[18] stages 11–19 (figs. 29–40).
- heart fusion of aortic and mitral endocardial cushion material^[19]
Respiratory - first generation of subsegmental bronchi now complete, see bronchial tree reconstruction^[20] (plates 3 and 4).
gastrointestinal tract - anal membrane defined.
renal - Cloacal membrane ruptures from urinary pressure at stage 18 or stage 19,
genital
- testis - Rete testis develops from the seminiferous cords at stages 19–23, and tunica albuginea forms.^[21].
- ovary - Rete ovarii cords are developing.^[22]
- uterus Müllerian duct grows independently from the invagination of the coelomic epithelium during stages 19-23^[16]
musculoskeletal
- Sternum right and left sternal bars are present.^[23] (figs. 7-17 and 7-22)
- Abdominal Wall segregation of the myoblasts into four distinct muscle groups with unidirectional orientation of myoblasts. Myoblast migrated over half of the distance to the ventral midline, abdominal wall thickest where the muscles migrated and the outermost layer of connective tissue comprises approximately half of the total thickness of the abdominal wall. Rectus muscle completely separated after migrating over half the distance to the midline.^[9]
neural
- rhombencephalon migration for olivary and arcuate nuclei begins.
- choroid plexus of the fourth ventricle present.
- stria medullaris thalami reaches the habenular nuclei.
- habenular commissure begins to develop.
- accessory olivary nucleus appears^[24]
- Neural - Vascular Development - middle cerebral artery becomes more prominent, the plexi fuse into a single artery and further branches pierce the cerebral hemisphere.^[5]

49

50

Stage 20

Head scalp vascular plexus visible

limb upper limbs begin to rotate ventrally

neural amygdaloid body has at least four individual nuclei^[24]

oculomotor nerve shows a dorsolateral and a ventromedial portion

rhombic lip (rhombencephalon) formation of the cerebellum (intermediate layer) and of the cochlear nuclei

cerebellum cell layer (future Purkinje cells) develops

choroid plexuses of the fourth and lateral ventricles

Eyelid the inner canthus is established.^[7]

51

gastrointestinal tract anal membrane perforates

52

Stage 21

neural cortical plate appears in the area of future insula^[25]

Neural - Vascular Development - formation of the anterior communicating artery.^[5]

limb upper and lower limbs rotate

Intraembryonic Coelom pericardioperitoneal canals close

Abdominal Wall Myoblasts have reached the ventral midline and myotubes were present and oriented uniformly within all muscle groups. The rectus abdominis formed distinct bundles of muscle. Connective tissue layers comprised the majority of the thickness of the abdominal wall, outermost layer of connective tissue accounted for the majority of this thickness.^[9]

53

54

Stage 22

neural neocortical fibres project to epithalamus, to dorsal thalamus, and to mesencephalon^[25]

limb fingers and toes lengthen

smell Stage 22 to early fetal period - migratory streams of neurons from the subventricular zone of the olfactory bulb towards the future claustrum^[6]

Uterus Vagina fused duct (uterovaginal canal) bifurcated at the caudal portion at Carnegie stages 22 and 23^[16]

55

Genital 8 Weeks Testis - mesenchyme, interstitial cells (of Leydig) secrete testosterone, androstenedione

Genital 8 to 12 Weeks - hCG stimulates testosterone production

Tongue Week 8 - nerves penetrate epitheilai basal lamina and synapse with undifferentiated, elongated, epithelial cells (taste bud progenitor cell)^[26]

56

Stage 23

Stage 23 defines the end of the embryonic (organogenesis) period

Mesoderm heart prominence, ossification continues

Head nose, eye, external acoustic meatus, eyelids, external ears, rounded head

Body - straightening of trunk, umbilical cord, intestines herniated at umbilicus

limb upper limbs longer and bent at elbow, hands and feet turned inward, foot with separated digits, wrist, hand with separated digits

Extraembryonic Coelom chorionic cavity is now lost by fusion with the expanding amniotic cavity

neural rhombencephalon, pyramidal decussation present, nuclei and tracts similar to those present in the newborn cerebellum present as only a plate connected to midbrain and hindbrain through fibre bundles^[27]

Axial Skeleton vertebral column 33 or 34 cartilaginous vertebrae (20-33 mm in total length), vertebral pedicles, articular and transverse processes identifiable (no spinous processes)^[28]

Abdominal Wall Rectus muscle forms 2 or 3 distinct layers with myotube orientation uniform in all muscles. The external oblique and internal oblique started to expand in thickness, transversus a thin layer of muscle.^[9]

Week 8

Stomach Week 8 - Gastrin containing cells in stomach antrum. Somatostatin cells in both the antrum and the fundus.

Genital - Female Development paired paramesonephric (Müllerian) ducts contact each other and are fused into a single tube that separates again and returns to the mesonephric (Wolffian) ducts. The paramesonephric ducts have not yet reached the urogenital sinus.^[16]

57-63

Week 9

Beginning of Fetal Development

**Historic Embryology**
	In 1949 the embryologist George Streeter^[29] used the replacement of cartilage within the humerus by bone marrow as an arbitrary definition of the embryo to fetus transition. "If the onset can be recognized in a given specimen, that specimen is straightway classed as a fetus."

CRL 43 mm, femur length 6 mm

9 weeks CRL 50 mm - genital genitalia in both sexes look identical^[30]

uterus - paramesonephric ducts come into apposition with the urorectal septum and begin to fuse

Day

Stage

Event

64

Gastrointestinal Tract Week 10 intestines in abdomen

Pituitary growth hormone and ACTH detectable

Pancreas Week 10 glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins

Tongue Week 10 shallow grooves above the taste bud primordium

Stomach Week 10 - Glucagon containing cells in stomach fundus.

Nail Development fingernails appear

outer ear Week 10 - Meatal plug extends in a disc-like fashion, the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. Proximal portion of the neck starts to be resorbed.

inner ear Week 10 - neural-crest-derived melanocytes migrate into the cochlea. They penetrate the basement membrane of the lateral wall epithelium and develop into the intermediate cells of the stria vascularis.^[31]

65

66

67

68

69

70

Week 10 - CRL 55 mm, femur length 9 mm, biparietal diameter 17 mm

Day

Stage

Event

neural - Cerebrum appearance of the first sulcus (week 11-15, GA 13-17 weeks)^[32]

71

Thyroid colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis

Stomach Week 11 - Serotonin containing cells in both the antrum and the fundus.

72

73

74

75

76

77

Week 11 - CRL 68 mm, femur length 12 mm, biparietal diameter 20 mm

Systems
Systems: bone timeline \| eye neural crest timeline \| heart abnormality timeline \| hearing EAM timeline \| muscle timeline \| ovary timeline \| placental villi timeline \| shoulder timeline \| smell timeline \| spleen timeline \| ventricular timeline

References

↑ ^1.0 ^1.1 ^1.2 O'Rahilly R & Müller F. (2007). The development of the neural crest in the human. J. Anat. , 211, 335-51. PMID: 17848161 DOI.
↑ ^2.0 ^2.1 O'Rahilly R & Müller F. (1990). Ventricular system and choroid plexuses of the human brain during the embryonic period proper. Am. J. Anat. , 189, 285-302. PMID: 2285038 DOI.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 Godlewski G, Gaubert-Cristol R, Rouy S & Prudhomme M. (1997). Liver development in the rat and in man during the embryonic period (Carnegie stages 11-23). Microsc. Res. Tech. , 39, 314-27. PMID: 9407542 <314::AID-JEMT2>3.0.CO;2-H DOI.
↑ Müller F & O'Rahilly R. (1988). The development of the human brain from a closed neural tube at stage 13. Anat. Embryol. , 177, 203-24. PMID: 3354839
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 Menshawi K, Mohr JP & Gutierrez J. (2015). A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply. J Stroke , 17, 144-58. PMID: 26060802 DOI.
↑ ^6.0 ^6.1 ^6.2 ^6.3 Müller F & O'Rahilly R. (2004). Olfactory structures in staged human embryos. Cells Tissues Organs (Print) , 178, 93-116. PMID: 15604533 DOI.
↑ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 Pearson AA. (1980). The development of the eyelids. Part I. External features. J. Anat. , 130, 33-42. PMID: 7364662
↑ ^8.0 ^8.1 Clugston RD, Zhang W & Greer JJ. (2010). Early development of the primordial mammalian diaphragm and cellular mechanisms of nitrofen-induced congenital diaphragmatic hernia. Birth Defects Res. Part A Clin. Mol. Teratol. , 88, 15-24. PMID: 19711422 DOI.
↑ ^9.0 ^9.1 ^9.2 ^9.3 ^9.4 ^9.5 ^9.6 Nichol PF, Corliss RF, Yamada S, Shiota K & Saijoh Y. (2012). Muscle patterning in mouse and human abdominal wall development and omphalocele specimens of humans. Anat Rec (Hoboken) , 295, 2129-40. PMID: 22976993 DOI.
↑ Müller F & O'Rahilly R. (1988). The first appearance of the future cerebral hemispheres in the human embryo at stage 14. Anat. Embryol. , 177, 495-511. PMID: 3377191
↑ Patelska-Banaszewska M & Woźniak W. (2005). The subarachnoid space develops early in the human embryonic period. Folia Morphol. (Warsz) , 64, 212-6. PMID: 16228957
↑ Müller F & O'Rahilly R. (1988). The development of the human brain, including the longitudinal zoning in the diencephalon at stage 15. Anat. Embryol. , 179, 55-71. PMID: 3213956
↑ Müller F & O'Rahilly R. (1989). The human brain at stage 16, including the initial evagination of the neurohypophysis. Anat. Embryol. , 179, 551-69. PMID: 2751117
↑ Müller F & O'Rahilly R. (1989). The human brain at stage 17, including the appearance of the future olfactory bulb and the first amygdaloid nuclei. Anat. Embryol. , 180, 353-69. PMID: 2802187
↑ ^15.0 ^15.1 Patelska-Banaszewska M & Woźniak W. (2004). The development of the epidural space in human embryos. Folia Morphol. (Warsz) , 63, 273-9. PMID: 15478101
↑ ^16.0 ^16.1 ^16.2 ^16.3 Hashimoto R. (2003). Development of the human Müllerian duct in the sexually undifferentiated stage. Anat Rec A Discov Mol Cell Evol Biol , 272, 514-9. PMID: 12740945 DOI.
↑ Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.
↑ Congdon ED. Transformation of the aortic-arch system during the development of the human embryo. (1922) Contrib. Embryol., Carnegie Inst. Wash. Publ 277, 14:47-110.
↑ Teal SI., Moore GW. and Hutchins GM. Development of aortic and mitral valve continuity in the human embryonic heart. (1986) Amer. J. Anat., 176:447-460.
↑ Wells LJ. Development of the human diaphragm and pleural sacs. (1954) Contrib. Embryol., Carnegie Inst. Wash. Publ. 603, 35: 107-134.
↑ Jirásek JE. Development of the Genital System and Male Pseudohermaphroditism. (1971) Johns Hopkins Press, Baltimore.
↑ Wilson KM. Origin and development of the rete ovarii and the rete testis in the human embryo. (1926) Carnegie Instn. Wash. Publ. 362, Contrib. Embryol., Carnegie Inst. Wash., 17:69-88.
↑ Gasser RL. Atlas of Human Embryos. (1975) Harper & Row, Hagerstown, Maryland.
↑ ^24.0 ^24.1 Müller F & O'Rahilly R. (1990). The human brain at stages 18-20, including the choroid plexuses and the amygdaloid and septal nuclei. Anat. Embryol. , 182, 285-306. PMID: 2268071
↑ ^25.0 ^25.1 Müller F & O'Rahilly R. (1990). The human brain at stages 21-23, with particular reference to the cerebral cortical plate and to the development of the cerebellum. Anat. Embryol. , 182, 375-400. PMID: 2252222
↑ Witt M & Reutter K. (1996). Embryonic and early fetal development of human taste buds: a transmission electron microscopical study. Anat. Rec. , 246, 507-23. PMID: 8955790 <507::AID-AR10>3.0.CO;2-S DOI.
↑ Müller F & O'Rahilly R. (1990). The human rhombencephalon at the end of the embryonic period proper. Am. J. Anat. , 189, 127-45. PMID: 2244584 DOI.
↑ O'Rahilly R, Muller F & Meyer DB. (1980). The human vertebral column at the end of the embryonic period proper. 1. The column as a whole. J. Anat. , 131, 565-75. PMID: 7216919
↑ Streeter GL. Developmental horizons in human embryos (fourth issue). A review of the histogenesis of cartilage and bone. (1949) Carnegie Instn. Wash. Publ. 583, Contrib. Embryol., 33: 149-169. PMID: 18144445
↑ Wünsch L & Schober JM. (2007). Imaging and examination strategies of normal male and female sex development and anatomy. Best Pract. Res. Clin. Endocrinol. Metab. , 21, 367-79. PMID: 17875485 DOI.
↑ Locher H, de Groot JC, van Iperen L, Huisman MA, Frijns JH & Chuva de Sousa Lopes SM. (2015). Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss. Dev Neurobiol , 75, 1219-40. PMID: 25663387 DOI.
↑ Afif A, Bouvier R, Buenerd A, Trouillas J & Mertens P. (2007). Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct , 212, 335-46. PMID: 17962979 DOI.

Glossary Links

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Cite this page: Hill, M.A. (2023, December 11) 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

What Links Here?

[PMID17848161-1] 1.0 ^1.1 ^1.2 O'Rahilly R & Müller F. (2007). The development of the neural crest in the human. J. Anat. , 211, 335-51. PMID: 17848161 DOI.

[PMID2285038-2] 2.0 ^2.1 O'Rahilly R & Müller F. (1990). Ventricular system and choroid plexuses of the human brain during the embryonic period proper. Am. J. Anat. , 189, 285-302. PMID: 2285038 DOI.

[PMID9407542-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 Godlewski G, Gaubert-Cristol R, Rouy S & Prudhomme M. (1997). Liver development in the rat and in man during the embryonic period (Carnegie stages 11-23). Microsc. Res. Tech. , 39, 314-27. PMID: 9407542 <314::AID-JEMT2>3.0.CO;2-H DOI.

[PMID3354839-4] Müller F & O'Rahilly R. (1988). The development of the human brain from a closed neural tube at stage 13. Anat. Embryol. , 177, 203-24. PMID: 3354839

[PMID26060802-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 Menshawi K, Mohr JP & Gutierrez J. (2015). A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply. J Stroke , 17, 144-58. PMID: 26060802 DOI.

[PMID15604533-6] 6.0 ^6.1 ^6.2 ^6.3 Müller F & O'Rahilly R. (2004). Olfactory structures in staged human embryos. Cells Tissues Organs (Print) , 178, 93-116. PMID: 15604533 DOI.

[PMID7364662-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 Pearson AA. (1980). The development of the eyelids. Part I. External features. J. Anat. , 130, 33-42. PMID: 7364662

[PMID19711422-8] 8.0 ^8.1 Clugston RD, Zhang W & Greer JJ. (2010). Early development of the primordial mammalian diaphragm and cellular mechanisms of nitrofen-induced congenital diaphragmatic hernia. Birth Defects Res. Part A Clin. Mol. Teratol. , 88, 15-24. PMID: 19711422 DOI.

[PMID22976993-9] 9.0 ^9.1 ^9.2 ^9.3 ^9.4 ^9.5 ^9.6 Nichol PF, Corliss RF, Yamada S, Shiota K & Saijoh Y. (2012). Muscle patterning in mouse and human abdominal wall development and omphalocele specimens of humans. Anat Rec (Hoboken) , 295, 2129-40. PMID: 22976993 DOI.

[PMID3377191-10] Müller F & O'Rahilly R. (1988). The first appearance of the future cerebral hemispheres in the human embryo at stage 14. Anat. Embryol. , 177, 495-511. PMID: 3377191

[PMID16228957-11] Patelska-Banaszewska M & Woźniak W. (2005). The subarachnoid space develops early in the human embryonic period. Folia Morphol. (Warsz) , 64, 212-6. PMID: 16228957

[PMID3213956-12] Müller F & O'Rahilly R. (1988). The development of the human brain, including the longitudinal zoning in the diencephalon at stage 15. Anat. Embryol. , 179, 55-71. PMID: 3213956

[PMID2751117-13] Müller F & O'Rahilly R. (1989). The human brain at stage 16, including the initial evagination of the neurohypophysis. Anat. Embryol. , 179, 551-69. PMID: 2751117

[PMID2802187-14] Müller F & O'Rahilly R. (1989). The human brain at stage 17, including the appearance of the future olfactory bulb and the first amygdaloid nuclei. Anat. Embryol. , 180, 353-69. PMID: 2802187

[PMID15478101-15] 15.0 ^15.1 Patelska-Banaszewska M & Woźniak W. (2004). The development of the epidural space in human embryos. Folia Morphol. (Warsz) , 63, 273-9. PMID: 15478101

[PMID12740945-16] 16.0 ^16.1 ^16.2 ^16.3 Hashimoto R. (2003). Development of the human Müllerian duct in the sexually undifferentiated stage. Anat Rec A Discov Mol Cell Evol Biol , 272, 514-9. PMID: 12740945 DOI.

[KeibelMall1912-17] Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

[Congdon1922-18] Congdon ED. Transformation of the aortic-arch system during the development of the human embryo. (1922) Contrib. Embryol., Carnegie Inst. Wash. Publ 277, 14:47-110.

[Teal1986-19] Teal SI., Moore GW. and Hutchins GM. Development of aortic and mitral valve continuity in the human embryonic heart. (1986) Amer. J. Anat., 176:447-460.

[Wells1954-20] Wells LJ. Development of the human diaphragm and pleural sacs. (1954) Contrib. Embryol., Carnegie Inst. Wash. Publ. 603, 35: 107-134.

[Jirasek1971-21] Jirásek JE. Development of the Genital System and Male Pseudohermaphroditism. (1971) Johns Hopkins Press, Baltimore.

[22] Wilson KM. Origin and development of the rete ovarii and the rete testis in the human embryo. (1926) Carnegie Instn. Wash. Publ. 362, Contrib. Embryol., Carnegie Inst. Wash., 17:69-88.

[Gasser1975-23] Gasser RL. Atlas of Human Embryos. (1975) Harper & Row, Hagerstown, Maryland.

[PMID2268071-24] 24.0 ^24.1 Müller F & O'Rahilly R. (1990). The human brain at stages 18-20, including the choroid plexuses and the amygdaloid and septal nuclei. Anat. Embryol. , 182, 285-306. PMID: 2268071

[PMID2252222-25] 25.0 ^25.1 Müller F & O'Rahilly R. (1990). The human brain at stages 21-23, with particular reference to the cerebral cortical plate and to the development of the cerebellum. Anat. Embryol. , 182, 375-400. PMID: 2252222

[PMID8955790-26] Witt M & Reutter K. (1996). Embryonic and early fetal development of human taste buds: a transmission electron microscopical study. Anat. Rec. , 246, 507-23. PMID: 8955790 <507::AID-AR10>3.0.CO;2-S DOI.

[PMID2244584-27] Müller F & O'Rahilly R. (1990). The human rhombencephalon at the end of the embryonic period proper. Am. J. Anat. , 189, 127-45. PMID: 2244584 DOI.

[PMID7216919-28] O'Rahilly R, Muller F & Meyer DB. (1980). The human vertebral column at the end of the embryonic period proper. 1. The column as a whole. J. Anat. , 131, 565-75. PMID: 7216919

[Streeter1949-29] Streeter GL. Developmental horizons in human embryos (fourth issue). A review of the histogenesis of cartilage and bone. (1949) Carnegie Instn. Wash. Publ. 583, Contrib. Embryol., 33: 149-169. PMID: 18144445

[PMID17875485-30] Wünsch L & Schober JM. (2007). Imaging and examination strategies of normal male and female sex development and anatomy. Best Pract. Res. Clin. Endocrinol. Metab. , 21, 367-79. PMID: 17875485 DOI.

[PMID25663387-31] Locher H, de Groot JC, van Iperen L, Huisman MA, Frijns JH & Chuva de Sousa Lopes SM. (2015). Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss. Dev Neurobiol , 75, 1219-40. PMID: 25663387 DOI.

[PMID17962979-32] Afif A, Bouvier R, Buenerd A, Trouillas J & Mertens P. (2007). Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct , 212, 335-46. PMID: 17962979 DOI.

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