Neural Crest Development

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Human embryo week 4 neural crest cells
Human embryo neural crest cells (Week 4, stage 11)

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, adrenal glands, gastrointestinal tract) will also have a contribution fron the neural crest cells. An in vitro study[1] has shown neural crest cell migration occurs at different rates along the embryo axis between Carnegie stage 11 to 13 in week 4.

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.

Historically identified as "neural crest" by Arthur Marshall in 1879.[2] (see history below and original article).

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
Historic Embryology - Neural Crest  
1879 Olfactory Organ | 1905 Cranial and Spinal Nerves | 1908 10 mm Peripheral | 1910 Mammal Sympathetic | 1920 Human Sympathetic | 1939 10 Somite Embryo | 1942 Origin | 1957 Adrenal

Some Recent Findings

Zebrafish neura crest model
1957 Adrenal The Developing Human, 8th edn.jpg Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders. (chapter links only work with a UNSW connection). * Nervous System * Pharyngeal Apparatus, Face, and Neck Larsen's human embryology 4th edn.jpg Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4th ed.). New York; Edinburgh: Churchill Livingstone. The following chapter links only work with a UNSW Library subscription * Chapter 10 - Development of the Peripheral Nervous System * Chapter 16 - Development of the Pharyngeal Apparatus and Face Additional Resources * Developmental Biology. 6th edition. The Neural Crest * Nelms BL, Labosky PA. Transcriptional Control of Neural Crest Development. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Available from: * Dupin E, Creuzet S, Le Douarin NM. The Contribution of the Neural Crest to the Vertebrate Body. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-. Available from:


Mouse neural crest (E10.5 ganglia Sox10)
* Understand the structures derived from ectoderm. * Understand the formation of neural folds. * Identify the initial location of neural crest cells in the trilaminar embryo. * Identify pathways of neural crest migration throughout the embryo. * To know the major tissues to which neural crest cells contribute. * To know how abnormalities in development that result from abnormal neural crest cell migration. * Understand how neural crest cells contribute to the pharyngeal arches and the head structures they form.

Neural Crest Derivatives

A key feature of neural crest is the migration into other embryonic tissues to form specific neural and non-neural populations and structures.

Cranial neural crest

* migration - dorsolaterally and into pharyngeal arches * craniofacial mesenchyme - cartilage, bone, cranial neurons, glia, and connective tissues of the face * pharyngeal arches and pouches - thymic cells, tooth odontoblasts, middle ear bones (ossicles), stria vascularis cells, and jaw (mandible)
Cochlea - Stria Vascularis
Mouse organ of corti 02.jpg Mouse organ of corti 04.jpg
Inner ear cochlea, showing the stria vascularis intermediate cells that are derived from neural crest.
Hearing - Inner Ear Development
Eye - Cornea
Human embryonic cornea Mouse eye neural crest cornea 01.jpg
Human embryonic cornea detail (Week 8, Carnegie stage 22) Mouse cornea layers
The adult eye cornea has three layers: an outer epithelium layer (ectoderm), a middle stromal layer of collagen-rich extracellular matrix between stromal keratocytes (neural crest) and an inner layer of endothelial cells (neural crest)

Vision - Cornea Development

Carotid body are chemoreceptors in the wall of the common carotid (3rd pharyngeal arch) [14][15]

Cardiac neural crest

  • migration - located between the cranial and trunk neural crests, overlapping the anterior portion of the vagal neural crest.
  • pharyngeal arches - (3,4,6) melanocytes, neurons, cartilage, and connective tissue
  • heart outflow tract - aortic arch/pulmonary artery septum, large arteries wall musculoconnective tissue

Neural Crest - Cardiac

Cardiac Neural Crest Migration

Cardiac Neural Crest Migration

Trunk neural crest

  • migration - two major pathways over somites (dorsolaterally) and between somite and neural tube (ventrolaterally)
  • dorsolateral - skin melanocytes
  • ventrolaterally - dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters

para-aortic body

(organ of Zuckerkandl, OZ) A neural crest derived chromaffin body, anatomically located at the bifurcation of the aorta or at the origin of the inferior mesenteric artery. Thought to act as a fetal regulator of blood pressure, secreting catecholamines into the fetal circulation.[16] In human, reaches its maximal size at 3 years of age and then regresses either by death, dispersion or differentiation.[17]

Named in 1901 by Emil Zuckerkandl (1849-1910) a Hungarian-Austrian anatomist at the University of Vienna.

Links: Cardiovascular System Development

Vagal and sacral neural crest

  • migration - ventrally into surrounding splanchnic mesenchyme of gastrointestinal tract
  • splanchnic mesenchyme - parasympathetic (enteric) ganglia of the gut

Development Overview

The following cranial and trunk data is based upon 185 serially sectioned staged (Carnegie) human embryos.[18]

Cranial Neural Crest

  • stage 9 - an indication of mesencephalic neural crest
  • stage 10 - trigeminal, facial, and postotic components
  • stage 11 - crest-free zones are soon observable in rhombomere 1, 3, and 5
  • stage 12 - rhombomeres 6 and 7 neural crest migrate to pharyngeal arch 3 and then rostrad to the truncus arteriosus
  • stage 13 - nasal crest and the terminalis-vomeronasal complex are last of the cranial crest to appear

stages 9-14 - otic vesicle primordium descends

Vagal Neural Crest

Recent research suggests that the vagal neural crest cells are a transitional population that has evolved between the head and the trunk, taking separate pathways to the both the heart and to the gut.[19][20]

Trunk Neural Crest

Spinal ganglia increase in number over time and are in phase with the somites, though not their centre. There are 3 migratory pathways: ventrolateral between dermatomyotome and sclerotome, ventromedial between neural tube and sclerotomes, and lateral between surface ectoderm and dermatomyotome.

  • stage 13 - about 19 present
  • stage 14 - about 33 present
  • stage 15-23 - 30–35 ganglia

Neck and Shoulder

A mouse study using individually labelled cells of postotic neural crest followed the development of the shoulder girdle (clavicle and scapula) that connects the upper limb to the axial skeleton.[21]

  • Clavicle is a neural crest-mesodermal structure, posterior dermal clavicle mesoderm.
  • Cryptic cell boundaries traverse apparently homogeneous skeleton of the neck and shoulders.
  • Bones and muscles code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey
  • Neural crest anchors the head onto the anterior lining of the shoulder girdle
  • Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton.
  • Skeleton identified as neural crest-derived is affected in human Klippel-Feil syndrome, Sprengel's deformity and Arnold-Chiari I/II malformation.

Skin Melanocytes

Melanoblast migration.png Mouse-melanoblast migration icon.jpg
Mouse melanocyte migration[22] Movie Mouse Skin - Melanoblast Migration E14.5[23]

Neural Crest Migration

A key event in neural crest development is migration from the original site that neural crest cells are generated (edge of the neural plate) to the different anatomical regions within the embryo.


  • complement component C3a - (C3a) acts as an autocrine diffusible chemotactic agent attracting NCC toward the self-secreted source.


  • versican - (VCAN, Chondroitin Sulfate Proteoglycan 2; Cspg2) an extracellular matrix proteoglycan that acts as both an inhibitor of NCC migration and as a guiding cue by forming exclusionary boundaries.[24]

Links: OMIM 118661


The paper by Marshall, Morphology of the Vertebrate Olfactory Organ (1879)[2], was historically the first time the term "neural crest" was used. In his own earlier papers he had referred to this as a "neural ridge" in describing development of the chicken embryo neural tube.

See paper text and his referenced comment:

"I take this opportunity to make a slight alteration in the nomenclature adopted in my former paper. I have there suggested the term neural ridge for the longitudinal ridge of cells which grows out from the reentering angle between the external epiblast and the neural canal, and from which the nerves, whether cranial or spinal, arise. Since this ridge appears before closure of the neural canal is effected, there are manifestly two neural ridges, one on either side ; but I have also applied the same term, neural ridge, to the single outgrowth formed by the fusion of the neural ridges of the two sides after complete closure of the neural canal is effected, and after the external epiblast has become completely separated from the neural canal. I propose in future to speak of this single median outgrowth as the neural crest, limiting the term neural ridge to the former acceptation. Thus, while there are two neural ridges, there is only one neural crest, a distinction that will be at once evident on reference to my former figures."

Links: Embryology History


  1. 1.0 1.1 <pubmed>18689800</pubmed> Cite error: Invalid <ref> tag; name "PMID18689800" defined multiple times with different content
  2. 2.0 2.1 Marshall A. The morphology of the vertebrate olfactory organ. (1879) Quarterly Journal of Microscopic Science. 19: 300–340.
  3. 3.0 3.1 Cox SG, Kim H, Garnett AT, Medeiros DM, An W & Crump JG. (2012). An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest. PLoS Genet. , 8, e1002938. PMID: 23028350 DOI.
  4. <pubmed>29108781</pubmed>
  5. Mimura S, Suga M, Okada K, Kinehara M, Nikawa H & Furue MK. (2016). Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells. Int. J. Dev. Biol. , 60, 21-8. PMID: 26934293 DOI.
  6. Causeret F, Ensini M, Teissier A, Kessaris N, Richardson WD, Lucas de Couville T & Pierani A. (2011). Dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structures. PLoS ONE , 6, e19367. PMID: 21552538 DOI.
  7. Betters E, Liu Y, Kjaeldgaard A, Sundström E & García-Castro MI. (2010). Analysis of early human neural crest development. Dev. Biol. , 344, 578-92. PMID: 20478300 DOI.
  8. Kulesa PM, Bailey CM, Kasemeier-Kulesa JC & McLennan R. (2010). Cranial neural crest migration: new rules for an old road. Dev. Biol. , 344, 543-54. PMID: 20399765 DOI.
  9. Lee G, Chambers SM, Tomishima MJ & Studer L. (2010). Derivation of neural crest cells from human pluripotent stem cells. Nat Protoc , 5, 688-701. PMID: 20360764 DOI.
  10. Green SA, Simoes-Costa M & Bronner ME. (2015). Evolution of vertebrates as viewed from the crest. Nature , 520, 474-482. PMID: 25903629 DOI.
  11. 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.
  12. 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.
  13. <pubmed>10683170</pubmed>
  14. Smith P, Scraggs M & Heath D. (1993). The development of the nerve network in the fetal human carotid body and its subsequent function in cardiac disease. Cardioscience , 4, 143-9. PMID: 8400021
  15. Hempleman SC & Warburton SJ. (2013). Comparative embryology of the carotid body. Respir Physiol Neurobiol , 185, 3-8. PMID: 22902512 DOI.
  16. WEST GB, SHEPHERD DM, HUNTER RB & MACGREGOR AR. (1953). The function of the organs of Zuckerkandl. Clin Sci , 12, 317-25. PMID: 13107111
  17. <pubmed>23078542</pubmed>
  18. O'Rahilly R & Müller F. (2007). The development of the neural crest in the human. J. Anat. , 211, 335-51. PMID: 17848161 DOI.
  19. <pubmed>20962585</pubmed>
  20. Bryan R. Kuo, Carol A. Erickson Vagal neural crest cell migratory behavior: A transition between the cranial and trunk crest. Volume 240, Issue 9, pages 2084–2100, September 2011 Dev Dynamics
  21. Matsuoka T, Ahlberg PE, Kessaris N, Iannarelli P, Dennehy U, Richardson WD, McMahon AP & Koentges G. (2005). Neural crest origins of the neck and shoulder. Nature , 436, 347-55. PMID: 16034409 DOI.
  22. Matsuoka T, Ahlberg PE, Kessaris N, Iannarelli P, Dennehy U, Richardson WD, McMahon AP & Koentges G. (2005). Neural crest origins of the neck and shoulder. Nature , 436, 347-55. PMID: 16034409 DOI.
  23. Mort RL, Hay L & Jackson IJ. (2010). Ex vivo live imaging of melanoblast migration in embryonic mouse skin. Pigment Cell Melanoma Res , 23, 299-301. PMID: 20067551 DOI.
  24. Szabó A, Melchionda M, Nastasi G, Woods ML, Campo S, Perris R & Mayor R. (2016). In vivo confinement promotes collective migration of neural crest cells. J. Cell Biol. , 213, 543-55. PMID: 27241911 DOI.


Trainor, P. (ed) Neural crest cells: evolution, development and disease. ISBN: 978-0-12-401730-6 ScienceDirect Nelms BL, Labosky PA. Transcriptional Control of Neural Crest Development. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. PMID 21452438


Bronner ME & Simões-Costa M. (2016). The Neural Crest Migrating into the Twenty-First Century. Curr. Top. Dev. Biol. , 116, 115-34. PMID: 26970616 DOI.

Green SA, Simoes-Costa M & Bronner ME. (2015). Evolution of vertebrates as viewed from the crest. Nature , 520, 474-482. PMID: 25903629 DOI.

Lee YH & Saint-Jeannet JP. (2011). Sox9 function in craniofacial development and disease. Genesis , 49, 200-8. PMID: 21309066 DOI.

Kish PE, Bohnsack BL, Gallina D, Kasprick DS & Kahana A. (2011). The eye as an organizer of craniofacial development. Genesis , 49, 222-30. PMID: 21309065 DOI.

Jiang M, Stanke J & Lahti JM. (2011). The connections between neural crest development and neuroblastoma. Curr. Top. Dev. Biol. , 94, 77-127. PMID: 21295685 DOI.

Nelms BL & Labosky PA. (2010). . , , . PMID: 21452438


O'Rahilly R & Müller F. (2007). The development of the neural crest in the human. J. Anat. , 211, 335-51. PMID: 17848161 DOI.

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