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.
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.
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Other Pages: Neural | Skin | Teeth | Head | Face | Heart | Endocrine - Adrenal Glands | Gastrointestinal Tract
Labelled neural crest cell migration at level of Rhombomere 4 into a pharyngeal arch. Additional neural crest migration movies by Paul Kulesa are available here
 Nrp1 and Sema3a expression patterns during trunk NCC migration |
Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification. Schwarz Q, Maden CH, Vieira JM, Ruhrberg C. Proc Natl Acad Sci U S A. 2009 Mar 26. [Epub ahead of print] PMID: 19325129 | PMCID: PMC2661313 | PNAS Link |
This PNAS paper describes a signaling pathway involved in the guidance of neural crest cells (NCC) in mice as they migrate throughout the embryo following 3 specific pathways. Two important concepts are that the SEMA3A and its receptor neuropilin 1 (NRP1) are repulsive guidance cues and the migration pathway did not appear to affect the specification , which differs from the concept of migration pathway specifying the neural crest cell differentiation pathway. (More? Molecular Development | Signaling | OMIM - SEMA3A - NRP1)
Blentic A, Tandon P, Payton S, Walshe J, Carney T, Kelsh RN, Mason I, Graham A. The emergence of ectomesenchyme. Dev Dyn. 2008 Jan 25;237(3):592-601
"...we show that neural crest cells stop expressing early neural crest markers upon entering the pharyngeal arches and switch to become ectomesenchymal. By contrast, those neural crest cells that do not enter the arches persist in their expression of early neural crest markers."
Neural Crest Abnormalities | Neural Crest early embryo (stage 13/14) | Neural Crest late embryo (stage 22) | Selected Human (stage 22) high power | Neural Crest Generation | Neural Crest Migration | Neural Movies
Embryo Images Unit: Neural Crest
(More? Research Labs)
For more detailed coverage of early neural development see Neural Notes - Development Overview.
Early Development and Neural Derivatives
Neural Crest Origin
Neural Crest Origin
Neural Crest - Differentiation
Studies using the chicken model demonstrated 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 progenitor cells migrate throughout the embryo and give rise to many different adult cells.
This Includes: ganglia cranial, dorsal root, sympathetic trunk, celiac, renal, plexus in GIT, glia, schwann cells, melanocytes (skin), and adrenal medulla (chromaffin cells).
In the head region neural crest also gives rise to a number of connective tissue structures.
Neural Crest - Head (see also Head Development Notes)
Mesencephalon and caudal Proencephalon
Mesencephalon and Rhombencephalon
Rhombencephalon
Neural Crest- Spinal Cord
Neural crest at the level of the body have two general migration pathways, defined by the position of the somite: a medial pathway (between the neural tube and the somite) and a lateral pathway (between the somite and the body wall).
Neural crest at the level of the head have a different migration pathway.
(More? Neural Crest Migration and Neural Movies)
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)
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).
Links: Journals | Online Textbooks | Search Textbooks | Reviews | Articles | 1999 Refs | Search PubMed | Glossary
Eurekah Bioscience Collection Chapters taken from the Eurekah Bioscience database. Eurekah.com and Landes Bioscience; 2003. Cranial Neural Crest and Development of the Head Skeleton
Search NLM Online Textbooks "neural crest" : Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach
Reviews
O'Rahilly R, Müller F. The development of the neural crest in the human. J Anat. 2007 Sep;211(3):335-51.
Anderson RB, Newgreen DF, Young HM Neural crest and the development of the enteric nervous system. Adv Exp Med Biol. 2006;589:181-96.
Huang R, Christ B, Patel K. Regulation of scapula development. Anat Embryol (Berl). 2006 Dec;211 Suppl 1:65-71.
Huber K. The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol. 2006 Oct 15;298(2):335-43.
Crane JF, Trainor PA. Neural crest stem and progenitor cells. Annu Rev Cell Dev Biol. 2006;22:267-86.
Articles
O'Rahilly R, Müller F. The development of the neural crest in the human. J Anat. 2007 Sep;211(3):335-51.
"The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions."
Ota KG, Kuraku S, Kuratani S. Hagfish embryology with reference to the evolution of the neural crest. Nature. 2007 April 5;446:672-5.
"We propose that the neural crest emerged as a population of de-epithelialized migratory cells in a common vertebrate ancestor, and suggest that the possibility of classical and molecular embryology in hagfish opens up new approaches to clarifying the evolutionary history of vertebrates."
Boulais N, Misery L. Merkel cells. J Am Acad Dermatol. 2007 Apr 3
High FA, Zhang M, Proweller A, Tu L, Parmacek MS, Pear WS, Epstein JA. An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007 Feb;117(2):353-63.
Brito JM, Teillet MA, Le Douarin NM. An early role for Sonic hedgehog from foregut endoderm in jaw development: Ensuring neural crest cell survival. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11607-12. Epub 2006 Jul 25. Hou L, Arnheiter H, Pavan WJ. Interspecies difference in the regulation of melanocyte development by SOX10 and MITF. Proc Natl Acad Sci U S A. 2006 103: 9081-9085
"The results may help to explain how some embryos, such as zebrafish, can achieve rapid pigmentation after fertilization, whereas others, such as mice, become pigmented only several days after birth."
Search Mar 2007 "neural crest development" 3,394 reference articles of which 692 were reviews. (More? Neural Crest Reviews References 1998)
Search PubMed: term = neural crest development |
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What an exciting embryonic tissue that has many adult derivatives but no equilivant. The evolution of these "wandering cells" has led to establishing a huge range of new tissues as well as cells contributing to many different tissues and systems throughout the entire embryo.
Neural crest coverage therefore can also be found within notes for other systems.
While the cells originate from the ectoderm layer, unlike the neural tube which "pinches off" from the surface ectoderm, the neural crest cells head off on migrations throughout the embryo forming a diverse range of cell types and contributions to different tissues.
This behaviour also means that failure of correct migration or differentiation can lead to a number of different abnormalities.
Please email Dr Mark Hill if you wish to make a comment about this current project.
These selected articles (April 2005) updated when time permits.
Mechanisms and perspectives on differentiation of autonomic neurons. Howard MJ., Dev Biol. 2005 Jan 15;277(2):271-86. Review. "Core of DNA binding proteins required for the development of sympathetic, parasympathetic, and enteric neurons, including Phox2 and MASH1, whose specificity is regulated by the recruitment of additional transcriptional regulators in a subtype-specific manner. For noradrenergic neurons, the basic helix-loop-helix DNA binding protein HAND2 (dHAND) appears to serve this function."
Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes. Hirobe T., Pigment Cell Res. 2005 Feb;18(1):2-12. Review. "Recent advances in the techniques of tissue culture and biochemistry have enabled us to clarify factors derived from keratinocytes. Alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone, basic fibroblast growth factor, nerve growth factor, endothelins, granulocyte-macrophage colony-stimulating factor, steel factor, leukemia inhibitory factor and hepatocyte growth factor have been suggested to be the keratinocyte-derived factors and to regulate the proliferation and/or differentiation of mammalian epidermal melanocytes."
Fgf15 is required for proper morphogenesis of the mouse cardiac outflow tract. Vincentz JW, McWhirter JR, Murre C, Baldini A, Furuta Y., Genesis. 2005 Apr;41(4):192-201. "Tbx1, a key regulator of pharyngeal arch development implicated in DiGeorge syndrome. In addition, Fgf15 and Tbx1 do not interact genetically, suggesting that Fgf15 operates through a pathway independent of Tbx1."
Xenopus Id3 is required downstream of Myc for the formation of multipotent neural crest progenitor cells. Light W, Vernon AE, Lasorella A, Iavarone A, Labonne C., Development. 2005 Apr;132(8):1831-1841. Fgf15 is required for proper morphogenesis of the mouse cardiac outflow tract. "show that the small HLH protein Id3 is a Myc target that plays an essential role in the formation and maintenance of neural crest stem cells."