1. Placode ectoderm and the neural crest:
development and derivatives
Dr. Altdorfer
neural crest, placods, head development, enteric nervous system, peripheral nervous system, quail-chick chimera

2.
login: educatio
pw: semmelweis

3. 3 week-old human embryo

4. Placode

5. Placodes and neural crest
Neural crest: caudal, medial, epithelio-mesenchymal transition
Placode: cranial, lateral, epithelialial tickenings
may form vesicles
Prof. Szél

6. Placode Derivative Neural plate Neural crest Ectoderm
Hypophyseal
Olfactory
Lens
Trigeminal
Otic
Epibranchial
Neural plate
Neural crest
Ectoderm
Rathke’s pouch Adenohypophysis
Olfactory epithelium
Lens
Trigeminal ggl. (partly)
Otic vesicle  membranous labyrinth, spiral+vestibular ggl.* (VIII.)
Epibranchial –> taste buds, geniculate ggl. (VII.), inf. ggl. of IX. and X. nerves*
Brain, spinal cord
ganglia, …
epidermis of skin,…
*Special sensory ganglia!

7. Cranial ganglia

8. Neural crest

9. 3 week-old human embryo

10. Neural crest cells are a multipotent progenitor population, so that the fates of specific crest populations must be controlled through environmental factors during normal development.
In the trunk region the neural crest cells are divided into two groups:
- Those which migrate dorsally, differentiate to melanocytes in the skin and hair follicles.
- migrating through the ventral pathway can form sensory ganglia and the accompanying glial satellite cells and Schwann cells (ventrolateral migration between the dermatomyotome and sclerotome cells of the somites),
or take the ventromedial pathway between sclerotome and neural tube and form sympathetic and enteric neurons, satellite cells, Schwann cells, and cells of the adrenal medulla.
The neural crest cells of the head region have more opportunities:
Neural derivatives:
- Sensory ganglia (General sensory ones):
-superior ganglia of the glossopharyngeal and vagus nerve,
-part of the trigeminal ganglion (other part: from placode).
Autonomic ganglia: ciliary (III.), pterygopalatine, submandibular (VII.)
and otic (IX.) ganglia (all these from 2nd rhombomer – located next to CN V. branches)
“ectomesenchymal” tissue:
-bones of the skull (frontal bone, parietal bone, squama of the temporal bone,
nasal bone, vomer, palatine bones, maxillae and mandible)
-all meninges , choroid and sclera of the eye
-dentin of the teeth
-connective tissue of the lacrimal, nasal, labial, palatine, oral, and salivary glands,
thyroid and parathyroid glands, and thymus
-connective tissue of the head (including melanocytes), cartilages, ligaments, and tendons
-Tunica media of the outflow tract of the heart and the great vessels (conotruncal septum)

11. NC cell migration in 3 streams:
‘trigeminal’ – around 3 divisions of CN V. (1st branchial arch*+frontonasal process)
‘hyoid’ – into 2. branchial arch
‘postotic’ (= behind otic vesicle) – into branchial arches 3-6.
Ectomesenchym: bones, cartilage, conn. tissue, vessels
* 2 of 3 auditory ossicles, jaw (Meckel’s cartilage)- skull… „new head”
Rhombomeres 1,2,(3) 
Rhombomeres (3),4,(5) 
Rhombomeres (5),6,7,8 

12. Neural crest cells give advantages to Vertebrates
Most of the morphological and functional differences between vertebrates and other chordates occur in the head and are derived embryologically from muscularized hypomere, neural crest, and epidermal (neurogenic) placodes. In the head, the neural crest functions as mesoderm and forms connective, skeletal, and muscular tissues. Both the neural crest and the epidermal placodes form special sense organs and other neural structures.
The transition to vertebrates apparently was associated with a shift from a passive to an active mode of predation, so that many of the features occurring only in vertebrates became concentrated in the head (Gans és Northcutt, Science 1983).
Plasticity of neural crest cells… ecto-mesenchyme
Characterictics of the vertebrate: „New Head”:
Special composite sense organs, complex visual organ is important in predation
Jaws for predation!
NC Pigment cells against UV radiation, accomodation to environment
Complex viscerocranium and chondrocranium development
(Neuron. 2003 Mar 27;37(6): A celebration of the new head and an evaluation of the new mouth.)

13. The peripheral nervous system

14. Derivatives of the neural crest
Ganglia, peripheral nerve cells
glial cells
Myofibroblast, fibroblast
Cartilage, bone
melanocytes
endocrine cells

15. Derivatives of the neural crest
peripheral nervous system
sympathetic, parasympathetic, sensory, enteric
Schwann cells, satellite cells
melanocytes
cartilage and bone in the head, smooth muscle, myofibroblast and fibroblast , mesectoderm
endocrine cells (adrenal medulla)
meninges
vessel wall (not endothelia) in the head region
Heart :
aortico-pulmonal, conotruncal septum

16. Results of chimera experiments, fate mapping studies -
derivatives of the neural crest
enteric nervous system
adrenal
medulla
N.M. Le Douarin / Mechanisms of Development 121 (2004) 1089–1102

17. Neural crest induction, current modell
Signals from ectoderm: BMP, Wnt
from mesoderm FGF-8 (amphibian data)
high conc. of BMP: epidermal ectoderm, low: neural ectoderm medium BMP concentration defines neural crest
Msx-1, Pax-3 expression starts (characteristic for NC cells)
snail-1 and slug (snail-2) expression starts which is needed for EMT (epithelio-mesenchymal transition)
slug is expressed at gastrulation as well!
Changes in adhesion properties (adhesion molecules)

18. Ectoderm/neuroectoderm specification

19. After induction: migration
ECM: Fibronectin, laminin, and type IV. collagen are favorable
ECM: chondroitin-sulfate: non-favorable
cell-surface integrins
TRUNK
HEAD
In the head region neural crest cells start the migration before the closure of the neural tube, not in the trunk

20. Neural crest divisions
Circumpharyngeal
pharynx
heart, great vessels
intestine
trunk
6th somite
cranial
sacral

21. Cranial
craniofacial (ecto-) mesenchyme, cartilage, bone, conn. tissue, nerve, glia
Topography
Cardiac
arterial wall, septum aorticopulmonale
Enteric
vagal, sacral, parasympathetic elements
Trunk
melanocytes, spinal ganglia, sympathetic ganglia
Prof. Szél

22. Neuromeres, prosomeres, rhombomeres

23. NC cell migration in 3 streams:
‘trigeminal’ – around 3 divisions of CN V. (1st branchial arch*+frontonasal process)
‘hyoid’ – into 2. branchial arch
‘postotic’ (= behind otic vesicle) – into branchial arches 3-6.
Ectomesenchym: bones, cartilage, conn. tissue, vessels
* 2 of 3 auditory ossicles, jaw (Meckel’s cartilage)- skull… „new head”
Rhombomeres 1,2,(3) 
Rhombomeres (3),4,(5) 
Rhombomeres (5),6,7,8 

24. In the pharyngeal region, the pathways of crest cell migration are
5th and 6th prosomere level do not give rise to neural crest only 1-4 prosomeres.
NC from hindbrain levels colonise 1st-3rd pharyngeal arches.
Each rhombomeric and mesencephalic crest cell „remember” to the segmental code.
In the pharyngeal region,
the pathways of crest cell migration are
closely correlated with Hoxb gene expr.
Cells of the cranial crest may be patterned with level –specific instructions, whereas cells of the
trunk crest are not.

26. Tooth development

27. NC partitipation in the ganglia

28. DiGeorge syndrome - hoxa-3 gene defect
Mesenchymal elements of cranialis crest (III-IV. pharyngeal arches) are defective
Aplasia of thymus and parathyroid gland (III-IV. pharyngeal pouch), „fish-mouth” deforation (shorter philtrum), deformation of lingual and cervical muscles, hypertelorism, mal-formations of the heart
Knockout mouse: short, thicke neck, lack of thymus and parathyroid gland, deformation of cardiac vessels and valves, deformation of greater horn of hyoid bone, cricoid cartilage, and epiglottis
Prof. Szél

29. The circumpharyngeal neural crest arises in the posterior rhombencephalic region, and in the lower part of the pharynx, emigrating circumpharyngeal crest cells pass behind the sixth pharyngeal arch.
Neural crest cells from the anterior rhombencephalon to the level of somite 5 emigrate from the circumpharyngeal crest as a stream, called the cardiac crest, toward the developing heart and aortic arches, whereas other neural crest cells from the levels of somites 1 to 7 constitute the vagal crest and migrate into the developing gut as precursors of the parasympathetic innervation of the digestive tract.

30. NC in heart development

31. Results of chimera experiments, fate mapping studies -
derivatives of the neural crest
enteric nervous system
adrenal
medulla
N.M. Le Douarin / Mechanisms of Development 121 (2004) 1089–1102

32. The enteric nervous system

33. 19-day old chicken embryo colon
Remak
ganglion
plexus
myentericus
plexus submucosus
Dr. Nagy

34. Hirschprung’s disease (megacolon congenitum aganglionare)
-developmental anomaly; Affects 1:5000 human infants.
complete absence of ENS in the distal bowel (no relaxation!); proximal colon becomes distended
90% are diagnosed as newborns.
Failure to pass stool within 1st 2 days of life, abdomen distended, vomiting
Dr. Nagy

35. Trunk neural crest Migratory pathways Prof. Szél ventrolateral pathway
(anterior somite: sensory ganglia)
dorsolateral pathway
(melanocytes)
ventral pathway
(sympathico-adrenal)
Prof. Szél

36. Migratory pathways

37. References
Schoenwolf, Bleyl, Brauer, Francis-West: Larsen’s Human Embryology, Elsevier
S. F. Gilbert: Developmental Biology, Sinauer associates, Inc. Publishers
T. W. Sadler: Langman’s Medical Embryology, Williams & Wilkins
B. M. Carlson: Human Embyology and Developmental Biology
Lectures of Anatomy Department (Prof. Szél Á., Prof. Csillag A., Prof. Kálmán M.
Dr. Nagy N., Dr. Kocsis K., Dr. H.-Minkó K.)
Neural regulation of human life processes – from the neuron to the behaviour. Interdisciplinary teaching material concerning the structure, function and clinical aspects of the nervous system for students of medicine, health and life sciences in Hungary
University of Pecs; Dialóg Campus Publishing-Nordex Kft.