Neural Crest Development
|Embryology - 17 Dec 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Neural Crest Migration
- 4 Textbooks
- 5 Objectives
- 6 Neural Crest Derivatives
- 7 Development Overview
- 8 Skin Melanocytes
- 9 Neural Crest Migration
- 10 Historic
- 11 References
- 12 Additional Images
- 13 Glossary Links
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 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.
|Neural Crest Links: Introduction | Lecture - Early Neural | Lecture - Neural Crest Development | Lecture Movie | Schwann | Adrenal Gland | Melanocyte | Peripheral Nervous System | Enteric Nervous System | Cornea | Cranial Nerves | Cardiac | Nicole Le Douarin | Neural Crest Movies | Abnormalities | Category:Neural Crest|
|Historic Embryology - Neural Crest|
|1879 Olfactory Organ | 1910 Mammal Sympathetic | 1920 Human Sympathetic | 1939 10 Somite Embryo|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Goran Radenkovic, Dina Radenkovic, Aleksandra Velickov Development of interstitial cells of Cajal in the human digestive tract as the result of reciprocal induction of mesenchymal and neural crest cells. J. Cell. Mol. Med.: 2017; PubMed 29193736
Silke Pauli, Ruchi Bajpai, Annette Borchers CHARGEd with neural crest defects. Am J Med Genet C Semin Med Genet: 2017; PubMed 29082625
Jean-Louis Plouhinec, Sofía Medina-Ruiz, Caroline Borday, Elsa Bernard, Jean-Philippe Vert, Michael B Eisen, Richard M Harland, Anne H Monsoro-Burq A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates. PLoS Biol.: 2017, 15(10);e2004045 PubMed 29049289
Ana Leonor Figueiredo, Frédérique Maczkowiak, Caroline Borday, Patrick Pla, Meghane Sittewelle, Caterina Pegoraro, Anne H Monsoro-Burq PFKFB4 control of Akt signaling is essential for premigratory and migratory neural crest formation. Development: 2017; PubMed 29038306
Embryonic Mouth Formation Explained. J Calif Dent Assoc: 2016, 44(10);608 PubMed 29035469
Neural crest formation stages and gene regulatory networks
|Neural Crest Origin|
| Peripheral Nervous System
| Neurons - sensory ganglia, sympathetic and parasympathetic ganglia, enteric nervous system, and plexuses
Neuroglial cells, olfactory ensheathing cells
Carotid body type I cells
|Integumentary||Epidermal pigment cells|
|Facial cartilage and bone||Facial and anterior ventral skull cartilage and bones|
|Sensory||Inner ear, corneal endothelium and stroma|
|Connective tissue|| Tooth papillae
smooth muscle, and adipose tissue of skin of head and neck
Connective tissue and smooth muscle in arteries of aortic arch origin
|Links: Neural Crest Development | Category:Neural Crest | Neural Crest collapsible table|
Neural Crest Migration
|Human neural crest cell migration (in vitro)
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.
Movie Source: Original Neural Crest movies kindly provided by Paul Kulesa.
|Neural crest migration Chicken Head (movies overview)|
- Neural Crest Movies: Migration 01 | Migration 02 | Migration 03 | Migration 04 | Migration 05 | Migration 06 | Migration 07
| Hill, M.A. (2017). UNSW Embryology (17th ed.) Retrieved December 17, 2017, from https://embryology.med.unsw.edu.au
|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).|
| 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
- 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|
|Inner ear cochlea, showing the stria vascularis intermediate cells that are derived from neural crest.|
|Eye - Cornea|
|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)|
Cardiac neural crest
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
(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.In human, reaches its maximal size at 3 years of age and then regresses either by death, dispersion or differentiation.
Named in 1901 by Emil Zuckerkandl (1849-1910) a Hungarian-Austrian anatomist at the University of Vienna.
Vagal and sacral neural crest
- migration - ventrally into surrounding splanchnic mesenchyme of gastrointestinal tract
- splanchnic mesenchyme - parasympathetic (enteric) ganglia of the gut
The following cranial and trunk data is based upon 185 serially sectioned staged (Carnegie) human embryos.
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.
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.
- 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.
|Mouse melanocyte migration||Movie Mouse Skin - Melanoblast Migration E14.5|
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. 
- Links: OMIM 118661
The paper by Marshall, Morphology of the Vertebrate Olfactory Organ (1879), 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
- Sophie Thomas, Marie Thomas, Patrick Wincker, Candice Babarit, Puting Xu, Marcy C Speer, Arnold Munnich, Stanislas Lyonnet, Michel Vekemans, Heather C Etchevers Human neural crest cells display molecular and phenotypic hallmarks of stem cells. Hum. Mol. Genet.: 2008, 17(21);3411-25 PubMed 18689800
- Marshall, A. Morphology of Vertebrate Olfactory Organ Quarterly Journal of Microscopic Science (1879) Vol. 19: 300–340. Cite error: Invalid
<ref>tag; name "Marshall1879" defined multiple times with different content
- Samuel G Cox, Hyunjung Kim, Aaron Timothy Garnett, Daniel Meulemans Medeiros, Woojin An, J Gage Crump An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest. PLoS Genet.: 2012, 8(9);e1002938 PubMed 23028350 | PLoS Genet.
- Sumiyo Mimura, Mika Suga, Kaori Okada, Masaki Kinehara, Hiroki Nikawa, Miho K Furue Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells. Int. J. Dev. Biol.: 2016; PubMed 26934293
- Frédéric Causeret, Monica Ensini, Anne Teissier, Nicoletta Kessaris, William D Richardson, Thibaut Lucas de Couville, Alessandra Pierani Dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structures. PLoS ONE: 2011, 6(4);e19367 PubMed 21552538
- Erin Betters, Ying Liu, Anders Kjaeldgaard, Erik Sundström, Martín I García-Castro Analysis of early human neural crest development. Dev. Biol.: 2010, 344(2);578-92 PubMed 20478300
- Paul M Kulesa, Caleb M Bailey, Jennifer C Kasemeier-Kulesa, Rebecca McLennan Cranial neural crest migration: new rules for an old road. Dev. Biol.: 2010, 344(2);543-54 PubMed 20399765
- Gabsang Lee, Stuart M Chambers, Mark J Tomishima, Lorenz Studer Derivation of neural crest cells from human pluripotent stem cells. Nat Protoc: 2010, 5(4);688-701 PubMed 20360764
- Stephen A Green, Marcos Simoes-Costa, Marianne E Bronner Evolution of vertebrates as viewed from the crest. Nature: 2015, 520(7548);474-82 PubMed 25903629 | Nature
- Perrine Barraud, Anastasia A Seferiadis, Luke D Tyson, Maarten F Zwart, Heather L Szabo-Rogers, Christiana Ruhrberg, Karen J Liu, Clare V H Baker Neural crest origin of olfactory ensheathing glia. Proc. Natl. Acad. Sci. U.S.A.: 2010, 107(49);21040-5 PubMed 21078992
- Ashwin Woodhoo, Lukas Sommer Development of the Schwann cell lineage: from the neural crest to the myelinated nerve. Glia: 2008, 56(14);1481-90 PubMed 18803317
- P M Kulesa, S E Fraser In ovo time-lapse analysis of chick hindbrain neural crest cell migration shows cell interactions during migration to the branchial arches. Development: 2000, 127(6);1161-72 PubMed 10683170
- P Smith, M Scraggs, D Heath The development of the nerve network in the fetal human carotid body and its subsequent function in cardiac disease. Cardioscience: 1993, 4(3);143-9 PubMed 8400021
- Steven C Hempleman, Stephen J Warburton Comparative embryology of the carotid body. Respir Physiol Neurobiol: 2013, 185(1);3-8 PubMed 22902512
- G B WEST, D M SHEPHERD, R B HUNTER, A R MACGREGOR The function of the organs of Zuckerkandl. Clin Sci: 1953, 12(4);317-25 PubMed 13107111
- Andreas Schober, Rosanna Parlato, Katrin Huber, Ralf Kinscherf, Björn Hartleben, Tobias B Huber, Günther Schütz, Klaus Unsicker Cell loss and autophagy in the extra-adrenal chromaffin organ of Zuckerkandl are regulated by glucocorticoid signalling. J. Neuroendocrinol.: 2013, 25(1);34-47 PubMed 23078542
- Ronan O'Rahilly, Fabiola Müller The development of the neural crest in the human. J. Anat.: 2007, 211(3);335-51 PubMed 17848161 | PMC2375817 | J Anat.
- Bryan R Kuo, Carol A Erickson Regional differences in neural crest morphogenesis. Cell Adh Migr: 2010, 4(4);567-85 PubMed 20962585
- 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
- Toshiyuki Matsuoka, Per E Ahlberg, Nicoletta Kessaris, Palma Iannarelli, Ulla Dennehy, William D Richardson, Andrew P McMahon, Georgy Koentges Neural crest origins of the neck and shoulder. Nature: 2005, 436(7049);347-55 PubMed 16034409 | PMC1352163| Nature
- Sarah E Millar An ideal society? Neighbors of diverse origins interact to create and maintain complex mini-organs in the skin. PLoS Biol.: 2005, 3(11);e372 PubMed 16277556 | PLoS Biol.
- Richard L Mort, Leonard Hay, Ian J Jackson Ex vivo live imaging of melanoblast migration in embryonic mouse skin. Pigment Cell Melanoma Res: 2010, 23(2);299-301 PubMed 20067551 | PMC2859249
- András Szabó, Manuela Melchionda, Giancarlo Nastasi, Mae L Woods, Salvatore Campo, Roberto Perris, Roberto Mayor In vivo confinement promotes collective migration of neural crest cells. J. Cell Biol.: 2016; PubMed 27241911
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
Marianne E Bronner, Marcos Simões-Costa The Neural Crest Migrating into the Twenty-First Century. Curr. Top. Dev. Biol.: 2016, 116;115-34 PubMed 26970616
Stephen A Green, Marcos Simoes-Costa, Marianne E Bronner Evolution of vertebrates as viewed from the crest. Nature: 2015, 520(7548);474-82 PubMed 25903629
Young-Hoon Lee, Jean-Pierre Saint-Jeannet Sox9 function in craniofacial development and disease. Genesis: 2011, 49(4);200-8 PubMed 21309066
Phillip E Kish, Brenda L Bohnsack, Donika Gallina, Daniel S Kasprick, Alon Kahana The eye as an organizer of craniofacial development. Genesis: 2011, 49(4);222-30 PubMed 21309065
Manrong Jiang, Jennifer Stanke, Jill M Lahti The connections between neural crest development and neuroblastoma. Curr. Top. Dev. Biol.: 2011, 94;77-127 PubMed 21295685
Ronan O'Rahilly, Fabiola Müller The development of the neural crest in the human. J. Anat.: 2007, 211(3);335-51 PubMed 17848161
Search Pubmed: Neural Crest Development
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Cite this page: Hill, M.A. 2017 Embryology Neural Crest Development. Retrieved December 17, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_Crest_Development
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