1. Andrea Heinzlmann Embryology Course 2018
NEURULATION
Andrea Heinzlmann
Embryology Course
2018

2. NEURULATION the process involved: in the formation of the neural plate
in the formation of the neural folds – closure of these folds to form the neural tube
these process are completed by the end of the 4th week
Development of the neural tube and the neural crest. The lateral edges of the neural plate are elevated and become the neural folds. The depressed midregion of the neural plate is called the neural groove. The neural folds continue to rise, appose in the midline and fuse to create the neural tube, which becomes covered by future epidermal ectoderm. As the neural folds rise and fuse, cells at the lateral border of the neuroectoderm (neural crest cells) begin to dissociate from their neighbours, undergo an epithelio-mesenchymal transition, and leave the neuroectoderm. 1: Surface ectoderm; 2: Neural plate; 3: Neural groove; 4: Neural crest; 5: Neural tube; 6: Spinal ganglion; 7: Anterior neuropore; 8: Posterior neuropore; 9: Notochord; 10: Primitive node; 11: Primitive streak; 12: Somites.

3. NEURAL PLATE AND NEURAL TUBE
as the notochord develops - induces the ectoderm to thicken and to form the NEURAL PLATE
NEUROECTODERM:
the ectoderm of the neural plate gives rise to:
the central nervous system
the retina
 The neural tube at roughly  the 28th day
The neural tube at roughly  the 29th day
 Neural plate at roughly  the 25th day
Neural plate: 19 – 23rd day
Neural plate Primitive streak Primitive nodes Neural groove
Neural tube Neural fold Neural groove Somites
Neural crest Protrusion of the pericardium Cranial neuropore Caudal neuropore
5 6 7
Somites Cut section of the amnion Neural folds

4. NEURAL PLATE AND NEURAL TUBE
at first the elongated neural plate corresponds in lenght to the undelying notochord
the neural plate appeares cranial to the primitive node
the neural plate appears dorsal to the notochord and to the adjacent mesoderm
the notochord elongates – the neural plate broadens – extends cranially as far as the oropharyngeal membrane
on day 18 the neural plate invaginates alog its central axis to form the NEURAL GROOVE (a median longitudinal groove)
 The neural tube at roughly  the 28th day
The neural tube at roughly  the 29th day
 Neural plate at roughly  the 25th day
Neural plate: 19 – 23rd day
Neural plate Primitive streak Primitive nodes Neural groove
Neural tube Neural fold Neural groove Somites
Neural crest Protrusion of the pericardium Cranial neuropore Caudal neuropore
5 6 7
Somites Cut section of the amnion Neural folds

5. NEURAL PLATE AND NEURAL TUBE
NEURAL GROOVE:
on its each side has NEURAL FOLDS
the neural folds prominent at the cranial part of the embryo – first signs of brain development
by the end of the 3rd week – the neural folds fuse together to form the NEURAL TUBE
 The neural tube at roughly  the 28th day
The neural tube at roughly  the 29th day
 Neural plate at roughly  the 25th day
Neural plate: 19 – 23rd day
Neural plate Primitive streak Primitive nodes Neural groove
Neural tube Neural fold Neural groove Somites
Neural crest Protrusion of the pericardium Cranial neuropore Caudal neuropore
5 6 7
Somites Cut section of the amnion Neural folds

6. NEURAL PLATE AND NEURAL TUBE
separates from the surface ectoderm
the free edges of the ectoderm fuse – the ectoderm becomes continuous over the neural tube and the back of the embryo
the surface ectoderm differentiate into the epidermis of the skin
neurulation is completed during the 4th week
 The neural tube at roughly  the 28th day
The neural tube at roughly  the 29th day
 Neural plate at roughly  the 25th day
Neural plate: 19 – 23rd day
Neural plate Primitive streak Primitive nodes Neural groove
Neural tube Neural fold Neural groove Somites
Neural crest Protrusion of the pericardium Cranial neuropore Caudal neuropore
5 6 7
Somites Cut section of the amnion Neural folds

7. NEURAL CREST FORMATION
1. as the neural folds fuse to form the neural tube 2. some neuroectodermal cells lying along the crest of each neural fold lose their epithelial affinities attaching to neighboring cells 3. as the neural tube separates separates from the surface ectoderm – these neural crest cells migrate dorsolaterally on each side of the neural tube - these cells from the NEURAL CREST between the neural tube and the ovarlying surface ectoderm
The neural tube at roughly  the 29th day
Neural crest Protrusion of the pericardium Cranial neuropore Caudal neuropore

8. NEURAL CREST FORMATION
1. separates into right and left parts – migrate in a wave to dorsolateral aspects of the neural tube
2. neural crest cells migrate within the mesenchyme

9. NEURAL CREST FORMATION
Neural crest after  a completed detachment (neural tube stage)
Migrating neural crest cells
(neural groove stage)
 The forming neural crest (neural plate stage)
A B 1 2 3
Neural plate stage Neural groove stage Epiblast Neural groove Neural crest
1 2 3
Epiblast Neural fold Migrating neural crest cells
4 5 6
Neuroepithelium Central canal  Neural tube

10. NEURAL CREST FORMATION
NEURAL CREST CELLS DIFFERENTIATE INTO:
spinal ganglia
ganglia of the autonomic nervous system
ganglia of cranial nerves V, VII, IX, X
sheates of the peripheral nerves
pia mater
arachnoid mater

11. DEVELOPMENT OF SOMITES
as the notochord and the neral tube form
the intraembryonic mesoderm on each side of the notochord and the neural tube proliferates to form the PARAXIAL MESODERM
each paraxial mesoderm is continous laterally with the INTERMEDIATE MESODERM
the intermediate mesoderm thins into a layer of LATERAL MESODERM
the lateral mesoderm continuous with the extraembryonic mesoderm
Paraxial mesoderm Intermediate mesoderm Lateral plate mesoderm Chordal process Amnion Intraembryonic coelom Endoblast Ectoblast Somatopleural (mesoderm and ectoderm) Splanchnopleural (mesoderm and endoderm) Neural groove Neural plate

12. DEVELOPMENT OF SOMITES
PARAXIAL MESODERM:
at the end of the 3rdweek differentiates and begins to divide into paired cuboidal bodies - SOMITES on each side of the developing neural tube
the 1st pair of somites appears at the end of the 3rd week near the cranial end of the notochors
pairs form in a carniocaudal sequence
 Appearance of the somitomeres,
at roughly the 25th day
Genesis of the intraembryonic coelom,
at roughly the 23rd day
 Evolution of the mesoblast
Endoblast Ectoblast Somatopleure with ectoblast Splanchnopleure with endoblast
Paraxial mesoderm Intermediate mesoderm Lateral plate mesoderm Neural groove Ectoblast Endoblast
Paraxial mesoblast Intermediate mesoblast Lateral plate mesoblast Chordal process Sectional edge of the amnion Intraembryonic coelom
Transverse section with a dorsal view at around the 25th day.
The cylindrical cell collections of the paraxial mesoderm segment
form the somitomeres (arrows).
The intermediate mesoblast is involved in the urogenital development.

13. DEVELOPMENT OF SOMITES
SOMITES gives rise to:
most of the axial skeleton (sclerotome)
associated muscles (myotome)
to the adjacent dermis of the skin (dermatome)

14. DEVELOPMENT OF INTRAEMBRYONIC COELOM (BODY CAVITIY)
appears first as a small, isolated coelomic spaces in the alteral mesoderm and cardiogenic mesoderm
these spaces coalesce to form a single cavity – the INTRAEMBRYONIC COELOM
The intraembryonic coelome divides the lateral mesoderm into:
a somatic or parietal layer (SOMATOPLEURA)
a splanchnic or visceral layer (SPLANCHNOPLEURA)
Mesoderm before the  vacuoles form on roughly the 20th day
Coelomic vacuoles at roughly the 23rd day
 Coelomic cavity at roughly  the 25th day
Lateral plate mesoderm Intermediate mesoderm Paraxial mesoderm Neural groove Coelomic vacuoles Intraembryonic coelom Extraembryonic coelom
Extraembryonic mesoblast Notochord  Splanchnopleure with endoderm Somatopleure with ectoderm Dorsal aorta (paired)
Paraxial mesoderm Intermediate mesoderm Lateral plate mesoderm Chordal process

15. DEVELOPMENT OF INTRAEMBRYONIC COELOM (BODY CAVITIY)
SOMATOPLEURA: - continous with the extraembryonic mesoder, which covers the amnion - the somatopleura and the overlying emryonic ectoderm form the body wall

16. DEVELOPMENT OF INTRAEMBRYONIC COELOM (BODY CAVITIY)
SPLANCHNOPLEURA: – continuous with the extraembryonic mesoderm, which covers the umbilical vesicle - the splanchnopleura and the underlying embryonic endoderm form the wall of the gut

17. DEVELOPMENT OF INTRAEMBRYONIC COELOM (BODY CAVITIY)
during the 2nd month the intraembryonic coelome divided into:
the pleural cavities
the pericardial cavity
the peritoneal cavity

18. DERIVATES OF MESODERM

19. FOLDING OF EMBRYO
the three germinal layers begin to differentiate and transform
the initially flat embryonic disk develops into a ”C”- shape like structure
the folding and genesis of the abdominal wall permits a delimitation of the embryo, that can now be clearly distinguished from the appending organs
the extraembryonic tissue went over into the intraembryonic tissue with no boundaries
the folding and the resulting formation of the abdominal wall lead to an enclosure of the mesoderm and the endoderm -they become surrounded by the ectoderm

20. FOLDING OF EMBRYO
Two mechanisms lead to the formation of the abdominal wall:
1. the cephalo-caudal flexion (in the longitudinal direction)
2. the lateral folding (in the transversal direction, rolling up)

21. FOLDING OF EMBRYO CEPHALO- CAUDAL FOLDING: FOLDING OF THE CRANIAL END:
rostral to the prechordal plate and the pharyngeal membrane, the mesenchymal cells form the cardiac plate (pericardium) and the septum transversum (which later becomes a part of the diaphragm and separates the coelom into thoracic and abdominal cavities)
with the 180° degree turn that results from the folding, the following occurs:  1. the pharyngeal membrane extends towards the lower front (mouth area)
2. the cardiogenic plate into the thorax are
3. between the cardiac anlage and the umbilical vesicle a mesenchymal bridge forms the septum transversum

22. FOLDING OF EMBRYO
CEPHALO- CAUDAL FOLDING: after this folding: 1. the brain (encephalon) lies the most cranially 2. followed by the mouth, heart, and diaphragm (septum transversum) during this folding: 3. the endoderm below the pharyngeal membrane becomes surrounded ventrally by the cardiac anlage - from this region, pharynx arises, the thyroid gland, the lungs, and the esophagus 4. the pharyngeal membrane that for now separates the mouth (ectoderm) from the throat (endoderm) later atrophies

23. FOLDING OF EMBRYO CEPHALO- CAUDAL FOLDING: Longitudinal folding
Carnegie stages
11a 11b a 14b 14c
Amniotic cavity Ectoblast  Umbilical vesicle Endoblast Endoblast that joins together  again under the notochord  Completely joined up endoblast Body stalk Allantois Lengthened allantois
18. Cardiac plate 19. Pericardial cavity 
11b a 14b 14c 15
Amniotic cavity Ectoblast  Umbilical vesicle Endoblast Endoblast that joins together  again under the notochord  Completely joined up endoblast
1. Amniotic cavity 2. Ectoblast  3. Umbilical vesicle 4a. Endoblast 4b. Endoblast that joins together  again under the notochord  4c. Completely joined up endoblast 5. Body stalk 6a. Allantois 6b. Lengthened allantois 7. Extraembryonic mesoblast 8. Cloacal membrane
9 10a 10b 11a 11b
Amniotic cavity Ectoblast  Umbilical vesicle Endoblast Endoblast that joins together 

24. FOLDING OF EMBRYO CEPHALO – CAUDAL FOLDING:
20. Fused neural tube 21. Septum transversum
20. Fused neural tube 21. Septum transversum 22. Closure of the neuroporus cranialis 23. Recessus caudalis 24. Thyroid gland anlage 25. Lung anlage 26. Liver anlage 27. Closure of the neuroporus caudalis 28. Dorsal aorta
Future prosencephalon Notochord Neural tube Pericardial cavity Cardiac tube Pharyngeal membrane
7 8 9
Extraembryonic mesoderm Throat Septum transversum

25. FOLDING OF EMBRYO CEPHALO – CAUDAL FOLDING: FOLDING OF THE CAUDAL END:
occurs after the cephalic folding
the body stalk comes closer to the umbilical vesicle (yolk sac)
the caudal end of the embryonic disk (with the cloacal membrane) comes to lie under the original embryonic disk 
the allantois and the body stalk come in the ventral direction, up to the umbilical vesicle (yolk sac) and merges with its stalk
Folding of the caudal end S9 (ca. 27th day)
Notochord Neural fold  Amniotic cavity Primitive streak Primary endoderm Cloacal membrane Allantois Body stalk
Notochord Neural tube Amniotic cavity  Endoderm Cloacal membrane Allantois Body stalk Hind gut

26. FOLDING OF EMBRYO LATERAL FOLDING:
at the same time as the cephalo-caudal flexion a lateral folding occurs 
this results in an enclosure of the endoderm by the ectoderm
IN A FIRST STEP:
the laterally lying structures, due to the large and rapid growth of the internal embryonic anlage (especially due to the disintegration of the somites), are shoved in a ventral direction
Some of the structures lying in the middle are then pressed against each other and fuse:
the pair of preformed aortae dorsales become the aorta mediana
for the medial section of the splanchnopleura that forms the dorsal mesenterium

27. FOLDING OF EMBRYO LATERAL FOLDING: IN A SECOND STEP:
1. the ectoderm of the caudal and cephalic ends of the embryo coalesce, due to the ventral folding along a medial line
 2. the amnion is pulled by the ectoderm
3. out of the small, dorsally-lying amniotic cavity a large one is thus created that surrounds the whole embryo and presses closely on the body stalk and the yolk sac - the umbilical cord is formed
4. the endoderm,becomes closed at both ends as well as along the side of the embryo, forms a tube (future for-, mid- and hindgut)
5. the midgut stands in an open connection to the umbilical vesicle (yolk sac) and the allantois - both structures later atrophy and are taken up in the umbilical cord
6. the connection between the embryo and extraembryonic appending organs remains up to the time of delivery - to permit the passage of the vital umbilical vessels located in the umbilical cord 
7. the intraembryonic coelom, a cavity between the splanchnopleura mesoderm (outer covering of the intestines) and the somatopleura mesoderm (inner covering of the trunk wall), which in the beginning is connected with the extraembryonic coelom (= chorionic cavity!), becomes separated from it by the folding and fusion of the lateral sides of the embryo. The intraembryonic coelom ring is formed

28. FOLDING OF EMBRYO LATERAL FOLDING:
Lateral folding in Carnegie stages 6 to 12
12. Central axial canal 13. Primitive node 14a. Ventrally merged notochord
14b. Ventrally resorbed notochord
9. Notochordal process 10a. Primitive streak 10b. Shrinking Primitive streak 11a. Neural plate
11b. Neural folds
29. Aortae
a 4b
Amniotic cavity Ectoderm Umbilical vesicle Endoderm Endoderm that joins together again under the notochorde 

29. FOLDING OF EMBRYO LATERAL FOLDING: 29 30 31 32 33 34 35 36 37
Aortae Umbilical veins Intraembryonic mesoderm Paraxial mesoderm Intermediate mesoderm Lateral plate mesoderm Canalis centralis Somite Nephrogenic cord

30. THANK YOU FOR YOUR ATTENTION!

31. BIBLIOGRAPHY
The developing human : clinically oriented embryology by Moore, Keith L Langman's Medical Embryology Thomas W. Sadler Essentials of Domestic Animal Embryology, 1st Edition, Poul Hyttel, Fred Sinowatz, Morten Vejlsted, Keith Betteridge

32. BIBLIOGRAPHY https://www.youtube.com/watch?v=EtWACeVEmKw