Lecture - Neural Crest Development

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Human embryo neural crest cells (Week 4, Carnegie stage 11)
Human embryo neural (Week 5, stage 14)

The neural crest are bilaterally paired strips of cells arising in the ectoderm at the margins of the neural tube. These cells migrate to many different locations and differentiate into many cell types within the embryo. This means that many different systems (neural, skin, teeth, head, face, heart, endocrine, gastrointestinal tract) will also have a contribution fron the neural crest cells.

In the body region, neural crest cells also contribute the peripheral nervous system (both neurons and glia) consisting of sensory ganglia (dorsal root ganglia), sympathetic and parasympathetic ganglia and neural plexuses within specific tissues/organs.

In the head region, neural crest cells migrate into the pharyngeal arches (as shown in movie below) forming ectomesenchyme contributing tissues which in the body region are typically derived from mesoderm (cartilage, bone, and connective tissue). General neural development is also covered in Neural Notes.

The term "neural crest was first used in Marshall AM. The morphology of the vertebrate olfactory organ. (1879) Quarterly Journal of Microscopic Science. 19: 300–340..

2018 Lecture - Print PDF

Lecture Objectives

Human Embryo (Carnegie stage 13) caudal trunk[1]
  • Understand the structures derived from ectoderm.
  • Identify the initial location of neural crest cells and pathways of neural crest migration throughout the embryo.
  • To know the major tissues to which neural crest cells contribute.
  • To know how abnormalities associated with neural crest cell.

Lecture Resources

 ‎‎Neural Crest 1
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Mouse cranial neural crest migration 01.jpg
 ‎‎Cranial Neural Crest
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Adrenal medulla.jpg
 ‎‎Adrenal Medulla
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Neural crest migration Chicken Head (movies overview)
 ‎‎Neural Crest 1
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 ‎‎Neural Crest 2
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 ‎‎Neural Crest 3
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 ‎‎Neural Crest 4
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 ‎‎Neural Crest 5
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 ‎‎Neural Crest 6
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 ‎‎Neural Crest 7
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UNSW Embryology logo
Hill, M.A. (2020). UNSW Embryology (20th ed.) Retrieved June 20, 2024, from https://embryology.med.unsw.edu.au
Neural Crest Links: neural crest | Lecture - Early Neural | Lecture - Neural Crest Development | Lecture Movie | Schwann cell | adrenal | melanocyte | peripheral nervous system | enteric nervous system | cornea | cranial nerve neural crest | head | skull | cardiac neural crest | Nicole Le Douarin | Neural Crest Movies | neural crest abnormalities | Category:Neural Crest
Student Projects 2023: 1 Patterning neural border and NC | 2 NPB NEUcrest | 3 EMT and NC | 4 miRNA and NC | 5 Adrenal Gland and NC | 6 Melanocyte & Melanoma | 7 Neurocristopathies | Neural Crest
These projects are the sole work of undergraduate science students and may contain errors in fact or descriptions.

Historic Embryology - Neural Crest  
1879 Olfactory Organ | 1905 Cranial and Spinal Nerves | 1908 10 mm Peripheral | 1910 Mammal Sympathetic | 1920 Human Sympathetic | 1928 Cranial ganglia | 1939 10 Somite Embryo | 1942 Origin | 1957 Adrenal
The Developing Human, 10th edn.jpg 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)
Larsen's human embryology 5th ed.jpg 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)
Additional Resources
2016 Lecture Video Recording  
This 2016 lecture video recording is similar in content to the current 2017 online lecture.

<html5media height="600" width="800">File:2016Lecture-Neural Crest.mp4</html5media>

Click to play new window - 2016 Lecture Video (48 MB)

Neural Crest Migration in the Head

<html5media height="380" width="410">File:Chicken-neural crest migration 01.mp4</html5media>

Click Here to play on mobile device

Chicken embryo sequence shows the migration of DiI-labeled neural crest cells towards the branchial arches as the embryo. White rings indicate migration of individual cells. Each image represents 10 confocal sections separated by 10 microns.

Early Development and Neural Derivatives

Neuralplate cartoon.png
  • bilaminar embryo- hypoblast
  • trilaminar embryo - ectoderm layer
    • neural plate - neural groove - neural tube and neural crest
  • cranial expansion of neural tube - central nervous system
  • caudal remainder of neural tube - spinal cord

Neural Crest - contributes both neural and non-neural cells

  • dorsal root ganglia
  • parasympathetic / sympathetic ganglia.
  • enteric ganglia

Neural Crest Origin

  • lateral region of neural plate
  • dorsal neural fold->tube

Two main embryo regions

  • Head (CNS level) - differentiate slightly earlier, mesencephalic region of neural folds.
  • Body (spinal cord level) - lateral edges of fused neural tube.

Neural Crest Generation

  • cranial region - Begins when still neural fold
  • spinal cord - from day 22 until day 26
    • after closure of caudal neuropore
    • rostro-caudal gradient of differentiation

Chicken model shows that they are not a segregated population. Interactions between the neural plate and epidermis can generate neural crest cells, since juxtaposition of these tissues at early stages results in the formation of neural crest cells at the interface.

At cranial levels, neuroepithelial cells can regulate to generate neural crest cells when the endogenous neural folds are removed, probably via interaction of the remaining neural tube with the epidermis.

Progenitor cells in the neural folds are multipotent, having the ability to form multiple ectodermal derivatives, including epidermal, neural crest, and neural tube cells the neural crest is an induced population that arises by interactions between the neural plate and the epidermis.

The competence of the neural plate to respond to inductive interactions changes as a function of embryonic age. (Text from: Bronner-Fraser M PNAS 1996 Sep 3;93(18):9352-7)

Neural Crest Derivatives

Note the major regional contributions in the simplified diagram below.

Neural crest contribution.jpg

Neural crest contribution[2]

Neural Crest Origin
System Cell Type
Peripheral Nervous System (PNS) Neurons - sensory ganglia, sympathetic and parasympathetic ganglia, enteric nervous system, and plexuses

Glia (neuroglial cells) - Schwann cells[3], satellite cells, olfactory ensheathing cells[4]

endocrine Adrenal medulla
Calcitonin-secreting cells
Carotid body type I cells
integumentary Epidermal pigment cells melanocyte
Facial cartilage and bone Facial and anterior ventral skull cartilage and bones
Sensory inner ear, cornea endothelium and stroma
Connective tissue tooth odontoblast

smooth muscle, and adipose tissue of skin in head and neck

Connective tissue of meninges, salivary, lachrymal, thymus, thyroid, and pituitary glands

Connective tissue and smooth muscle in arteries of aortic arch origin

Links: neural crest | Category:Neural Crest | Neural Crest collapsible table

Neural Crest - Head

See also Lecture - Head Development

Eye Development
Mouse E10.5- neural crest cell distribution (black)
Human embryo neural (Week 5, stage 14)

Mesencephalon and caudal Proencephalon

  • parasympathetic ganglia CN III
  • connective tissue around eye and nerve
  • head mesenchyme
  • neural connective tissue (meninges)

Mesencephalon and Rhombencephalon

  • pharayngeal arches
    • look at practical notes on neck and head.
  • cartilage rudiments (nose, face, middle ear)
  • face and facial skeleton
  • dermis, smooth muscle and fat
  • odontoblasts of developing teeth


  • C cells of thyroid
  • cranial nerve ganglia
  • neurons and glia
  • parasympathetic of VII, IX, X
  • sensory ganglia of V, VII, VIII, IX, X

Neural Crest - Peripheral Nervous System

  • peripheral nervous system
  • dorsal root ganglia (sensory N)
  • parasympathetic ganglia
  • sympathetic ganglia
  • enteric ganglia
  • motoneurons in both ganglia
  • all associated glia
Smooth muscle histology 002.jpg

Enteric nervous system

Neural Crest Migration


Hindbrain neural crest migration.jpg Mouse head E9-neural crest GFP.jpg Mouse-E9.5-Sox10.jpg
Hindbrain neural crest migration Mouse head E9 neural crest GFP Mouse E9.5 Sox10
Neural crest migration in the head in chicken (chicken neural crest movies overview)
Chicken-neural-crest-migration-01.jpg Chicken-neural-crest-migration-02.jpg Chicken-neural-crest-migration-03.jpg Chicken-neural-crest-migration-04.jpg Chicken-neural-crest-migration-05.jpg Chicken-neural-crest-migration-06.jpg Chicken-neural-crest-migration-07.jpg


Cardiac Outflow Tract

Cardiac Neural Crest Migration.jpg

Human neural crest cell migration (in vitro)[1]

Figure 13.2. Neural crest cell migration in the trunk of the chick embryo

  • Neural crest at the level of the body have two general migration pathways, defined by the position of the somite
    • medial pathway - between the neural tube and the somite
    • lateral pathway - between the somite and the body wall (cardiac NCC)
  • Neural crest cells (NCC) in mice guidance show migrate 3 specific pathways.
    • SEMA3A and its receptor neuropilin 1 (NRP1) - act as repulsive guidance cues
    • migration pathway did not affect specification - differs from the concept of migration pathway specifying the neural crest cell differentiation pathway

Neural crest at the level of the head have a different migration pathway. Figure 13.7. Cranial neural crest cell migration in the mammalian head

Sympathetic Ganglia and Adrenal Medulla

<html5media height="500" width="560">File:Adrenal medulla.mp4</html5media> Adrenal medulla.jpg The chromatin cells that populate the adrenal medulla are NCC.

Enteric nervous system

Vagal neural crest cells
  • transition between head and trunk NCC populations
  • level of somites 1-7
    • somite-levels 1-3 cardiac crest
  • take separate pathways to the gut and heart
    • ventral pathway - enteric (ENS)
    • dorsolateral pathway - cardiac
  • cell adhesive interactions within the gut sort NCC
    • core - neurons
    • shell - mesenchymal precursor/glia-like enteric neural crest
Smooth muscle histology 002.jpg

Myenteric plexus of the gut wall

Neural crest cell enteric sorting.jpg

Enteric neuron (red) and glia (blue) aggregation.[5]

Links: Enteric Nervous System | Figure 1. Mouse E10 embryo origins of NCCs for GIT

Historic Migration Experiments

Key early experiments in understanding the pattern of neural crest migration were carried out by LeDouarin in the 1980's (see Development of the peripheral Nervous system from the neural crest, Ann Rev Cell Biol 4 p375) Quail-Chick Chimeras | Figure 1.11. Neural crest cell migration Chimera experiment

These transplantation studies in chicken/quail chimeras utilised the different nucleoli appearance of cells to differentiate different species. Thus transplanation and subsequent histological processing allowed identification of the migration path and final destination of transplanted neural crest cells.

Similar later experiments have now been carried out using the neural crest cells molecularly tagged with (LacZ).




Neuroblastoma is the most common childhood cancer diagnosed before the age of 1 year, and accounts for 10 to 15% of all cancer deaths in children arising initially from the adrenal or other tissues.

Childhood cancer survival rates.jpg

Childhood cancer survival rates

Neuroblastoma | OMIM - Neuroblastoma

Digeorge Syndrome (DGS)

Digeorge chromosome22.jpg

Digeorge chromosome 22

  • DiGeorge syndrome is the most frequent microdeletion syndrome in humans caused by a hemizygous deletion (1.5 to 3.0-Mb) of chromosome 22q11.2.
  • Velo-cardio-facial syndrome, Hypoplasia of thymus and parathyroids, third and fourth pharyngeal pouch syndrome.
  • Abnormalities: cardiovascular, thymic and parathyroid, craniofacial anomalies, renal anomalies, hypocalcemia and immunodeficiency.

Intestinal Aganglionosis

Megacolon surgery.gif Megacolon stoma.gif

  • Intestinal Aganglionosis, Hirschsprung's Disease or Megacolon
  • lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).
  • severity is dependent upon the amount of the GIT that lacks intrinsic ganglia, due to developmental lack of neural crest migration into those segments.
  • first indication in newborns is an absence of the first bowel movement, other symptoms include throwing up and intestinal infections.
  • Clinically this is detected by one or more tests (barium enema and x ray, manometry or biopsy) and can currently only be treated by surgery. A temoporary ostomy (Colostomy or Ileostomy) with a stoma is carried out prior to a more permanent pull-through surgery.



  • In Australia each year 8,800 people are diagnosed with melanoma, and almost 1000 people die (Data, Cancer Council Australia).
  • Two different findings on the reprogramming of melanoma cells, which have a neural crest origin, when transplanted between species into embryos.

Melanoma staging

Neurofibromatosis Type 1 (NF1)

  • Neurofibromatosis Type 1 (von Recklinghausen) occurs in 1 in 3,000 to 4,000 people with characteristic skin blemishes forming in early childhood.
  • Multiple café-au-lait spots (flat skin patches darker than the surrounding area) appear in early childhood which increase in both size and number with age.
  • tumors can develop along nerves in the skin, brain, and other parts of the body. In the iris of the eye, Lisch nodules (benign growths) also appear
(French, café-au-lait = coffee with milk)

Atlas of Genetics and Cytogenetics in Oncology- Neurofibroma

Tetralogy of Fallot

Cardiac abnormality possibly stemming from abnormal neural crest migration. Named after Etienne-Louis Arthur Fallot (1888) who described it as "la maladie blue". (More? Cardiovascular System Development | Cardiac Tutorial | Lecture - Heart | Cardiovascular System - Abnormalities)

Treacher Collins syndrome

(TCS) A genetic developmental abnormality results from autosomal dominant mutations of the gene TCOF1 encoding the protein Treacle, identified in 2006. The syndrome is characterized by hypoplasia of the facial bones, cleft palate, and middle and external ear defects. These defects may relate to the effects on neural crest migration. (More? Neural Crest Development | OMIM - TCOF1 | PMID: 8563749)


  1. 1.0 1.1 Thomas S, Thomas M, Wincker P, Babarit C, Xu P, Speer MC, Munnich A, Lyonnet S, Vekemans M & Etchevers HC. (2008). Human neural crest cells display molecular and phenotypic hallmarks of stem cells. Hum. Mol. Genet. , 17, 3411-25. PMID: 18689800 DOI.
  2. Simões-Costa M & Bronner ME. (2013). Insights into neural crest development and evolution from genomic analysis. Genome Res. , 23, 1069-80. PMID: 23817048 DOI.
  3. Woodhoo A & Sommer L. (2008). Development of the Schwann cell lineage: from the neural crest to the myelinated nerve. Glia , 56, 1481-90. PMID: 18803317 DOI.
  4. Barraud P, Seferiadis AA, Tyson LD, Zwart MF, Szabo-Rogers HL, Ruhrberg C, Liu KJ & Baker CV. (2010). Neural crest origin of olfactory ensheathing glia. Proc. Natl. Acad. Sci. U.S.A. , 107, 21040-5. PMID: 21078992 DOI.
  5. Rollo BN, Zhang D, Simkin JE, Menheniott TR & Newgreen DF. (2015). Why are enteric ganglia so small? Role of differential adhesion of enteric neurons and enteric neural crest cells. F1000Res , 4, 113. PMID: 26064478 DOI.

Online Textbooks

Neural Crest Experiments: Figure 1.11. Neural crest cell migration Chimera experiment | Figure 13.5. Pluripotency of trunk neural crest cells


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Marshall AM. The morphology of the vertebrate olfactory organ. (1879) Quarterly Journal of Microscopic Science. 19: 300–340.


External Links

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 2018 ANAT2341 - Timetable | Course Outline | Moodle | Tutorial 1 | Tutorial 2 | Tutorial 3

Labs: 1 Preimplantation and Implantation | 2 Reproductive Technology Revolution | 3 Group Projects | 4 GM manipulation mouse embryos | 5 Early chicken eggs | 6 Female reproductive tract | 7 Skin regeneration | 8 Vertebral development | 9 Organogenesis Lab | 10 Cardiac development | 11 Group projects | 12 Stem Cell Journal Club

Lectures: 1 Introduction | 2 Fertilization | 3 Week 1/2 | 4 Week 3 | 5 Ectoderm | 6 Placenta | 7 Mesoderm | 8 Endoderm | 9 Research Technology | 10 Cardiovascular | 11 Respiratory | 12 Neural crest | 13 Head | 14 Musculoskeletal | 15 Limb | 16 Renal | 17 Genital | 18 Endocrine | 19 Sensory | 20 Fetal | 21 Integumentary | 22 Birth | 23 Stem cells | 24 Revision

 Student Projects: Group Projects Information Project 1 | Project 3 | Project 4 | Project 5 | 2018 Test Student | Copyright