Neural Crest Development

Embryology - 5 Dec 2023        Expand to Translate
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Introduction

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

Nicole Le Douarin

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.

Nicole Le Douarin has had a long research career, mainly on the development of neural crest cells using originally a Chicken-Quail chimera model she had developed, see also her recent review paper on the "beginnings" of the neural crest.

Historic Embryology

Arthur Milnes Marshall (1852–1893) at Cambridge in 1879 historically first described this embryonic region. In his study of dogfish and chicken brain development, and identified it as "neural crest". See neural crest history and the original 1879 article. Wilhelm His (1831-1904) in 1868 also described in the chick embryo the early neural structure that would form neural crest.

Use the links listed below to study development of specific neural crest populations.

Some Recent Findings

Zebrafish neura crest model

The mechanosensitive channel Piezo1 cooperates with Semaphorin to control neural crest migration "We identify that Piezo1 is required for the migration of Xenopus cephalic NC. We show that loss of Piezo1 promotes focal adhesion turnover and cytoskeletal dynamics by controlling Rac1 activity, leading to increased speed of migration. Moreover, overactivation of Rac1, due to Piezo1 inhibition, counteracts cell migration inhibitory signals by Semaphorins 3A and 3F, generating aberrant neural crest invasion in vivo. Thus, we find that, for directional migration in vivo, neural crest cells require a tight regulation of Rac1, by Semaphorins and Piezo1. We reveal here that a balance between a myriad of signals through Rac1 dictates cell migration in vivo, a mechanism that is likely to be conserved in other cell migration processes." Nubp2 is required for cranial neural crest survival in the mouse "The N-ethyl-N-nitrosourea (ENU) forward genetic screen is a useful tool for the unbiased discovery of novel mechanisms regulating developmental processes. We recovered the dorothy mutation in such a screen designed to recover recessive mutations affecting craniofacial development in the mouse. Dorothy embryos die prenatally and exhibit many striking phenotypes commonly associated with ciliopathies, including a severe midfacial clefting phenotype. We used exome sequencing to discover a missense mutation in nucleotide binding protein 2 (Nubp2) to be causative. This finding was confirmed by a complementation assay with the dorothy allele and an independent Nubp2 null allele (Nubp2null). We demonstrated that Nubp2 is indispensable for embryogenesis. NUBP2 is implicated in both the cytosolic iron/sulfur cluster assembly pathway and negative regulation of ciliogenesis. Conditional ablation of Nubp2 in the neural crest lineage with Wnt1-cre recapitulates the dorothy craniofacial phenotype. Using this model, we found that the proportion of ciliated cells in the craniofacial mesenchyme was unchanged, and that markers of the SHH, FGF, and BMP signaling pathways are unaltered. Finally, we show evidence that the phenotype results from a marked increase in apoptosis within the craniofacial mesenchyme." Evolution of the new head by gradual acquisition of neural crest regulatory circuits "The neural crest, an embryonic stem-cell population, is a vertebrate innovation that has been proposed to be a key component of the 'new head', which imbued vertebrates with predatory behaviour1,2. Here, to investigate how the evolution of neural crest cells affected the vertebrate body plan, we examined the molecular circuits that control neural crest development along the anteroposterior axis of a jawless vertebrate, the sea lamprey. Gene expression analysis showed that the cranial subpopulation of the neural crest of the lamprey lacks most components of a transcriptional circuit that is specific to the cranial neural crest in amniotes and confers the ability to form craniofacial cartilage onto non-cranial neural crest subpopulations3. Consistent with this, hierarchical clustering analysis revealed that the transcriptional profile of the lamprey cranial neural crest is more similar to the trunk neural crest of amniotes. Notably, analysis of the cranial neural crest in little skate and zebrafish embryos demonstrated that the transcriptional circuit that is specific to the cranial neural crest emerged via the gradual addition of network components to the neural crest of gnathostomes, which subsequently became restricted to the cephalic region. Our results indicate that the ancestral neural crest at the base of the vertebrate lineage possessed a trunk-like identity. We propose that the emergence of the cranial neural crest, by progressive assembly of an axial-specific regulatory circuit, allowed the elaboration of the new head during vertebrate evolution."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. 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. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Neural Crest Embryology |Neural Crest Development | Neural Crest

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. A genome-wide assessment of the ancestral neural crest gene regulatory network "The neural crest (NC) is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional and epigenomic profiles of NC cells in the sea lamprey, in order to gain insight into the ancestral state of the NC gene regulatory network (GRN). Transcriptome analyses identify clusters of co-regulated genes during NC specification and migration that show high conservation across vertebrates but also identify transcription factors (TFs) and cell-adhesion molecules not previously implicated in NC migration. ATAC-seq analysis uncovers an ensemble of cis-regulatory elements, including enhancers of Tfap2B, {{}}SoxE1 and Hox-α2 validated in the embryo. Cross-species deployment of lamprey elements identifies the deep conservation of lamprey SoxE1 enhancer activity, mediating homologous expression in jawed vertebrates. Our data provide insight into the core GRN elements conserved to the base of the vertebrates and expose others that are unique to lampreys." Migratory Neural Crest Cells Phagocytose Dead Cells in the Developing Nervous System{{#pmid:31495570|PMID31495570}} "During neural tube closure and spinal cord development, many cells die in both the central and peripheral nervous systems (CNS and PNS, respectively). However, myeloid-derived professional phagocytes have not yet colonized the trunk region during early neurogenesis. How apoptotic cells are removed from this region during these stages remains largely unknown. Using live imaging in zebrafish, we demonstrate that neural crest cells (NCCs) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Additionally, NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCCs phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment toward cellular debris is mediated by interleukin-1β. Taken together, our results reveal a role for NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes." apoptosis Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve Development "Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets.... Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve." heart The neural border: Induction, specification and maturation of the territory that generates neural crest cells "The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions." Review - Development of interstitial cells of Cajal in the human digestive tract as the result of reciprocal induction of mesenchymal and neural crest cells "Neural crest cells (NCC) can migrate into different parts of the body and express their strong inductive potential. In addition, they are multipotent and are able to differentiate into various cell types with diverse functions. In the primitive gut, NCC induce differentiation of muscular structures and interstitial cells of Cajal (ICC), and they themselves differentiate into the elements of the enteric nervous system (ENS), neurons and glial cells. ICC develop by way of mesenchymal cell differentiation in the outer parts of the primitive gut wall around the myenteric plexus (MP) ganglia, with the exception of colon, where they appear simultaneously also at the submucosal border of the circular muscular layer around the submucosal plexus (SMP) ganglia. ...Under the impact of stem cell factor (SCF), a portion of c-kit positive precursors lying immediately around the ganglia differentiate into ICC, while the rest differentiate into SMC." Enteric Nervous System Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells "The enteric nervous system arises from neural crest cells that migrate as chains into and along the primitive gut, subsequently differentiating into enteric neurons and glia. Little is known about the mechanisms governing neural crest migration en route to and along the gut in vivo. Here, we report that Retinoic Acid (RA) temporally controls zebrafish enteric neural crest cell chain migration. In vivo imaging reveals that RA loss severely compromises the integrity and migration of the chain of neural crest cells during the window of time window when they are moving along the foregut. After loss of RA, enteric progenitors accumulate in the foregut and differentiate into enteric neurons, but subsequently undergo apoptosis resulting in a striking neuronal deficit. Moreover, ectopic expression of the transcription factor meis3 and/or the receptor ret, partially rescues enteric neuron colonization after RA attenuation. Collectively, our findings suggest that retinoic acid plays a critical temporal role in promoting enteric neural crest chain migration and neuronal survival upstream of Meis3 and RET in vivo." Retinoic acid | zebrafish Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells "Neural crest (NC) cells are a group of cells located in the neural folds at the boundary between the neural and epidermal ectoderm. Cranial NC cells migrate to the branchial arches and give rise to the majority of the craniofacial region, whereas trunk and tail NC cells contribute to the heart, enteric ganglia of the gut, melanocytes, sympathetic ganglia, and adrenal chromaffin cells. ...These BMP4-treated NC cells were capable of differentiation into osteocytes and chondrocytes. The results of the present study indicate that BMP4 regulates cranial positioning during NC development." Bone Morphogenetic Protein An essential role of variant histone h3.3 for ectomesenchyme potential of the cranial neural crest "The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. ...Surprisingly, embryo-wide expression of dominant mutant H3.3 had little effect on embryonic development outside CNC, indicating an unexpectedly specific sensitivity of CNC to defects in H3.3 incorporation. Whereas previous studies had implicated H3.3 in large-scale histone replacement events that generate totipotency during germ line development, our work has revealed an additional role of H3.3 in the broad potential of the ectoderm-derived CNC, including the ability to make the mesoderm-like ectomesenchymal precursors of the head skeleton." Dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structures "Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. ... Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner." Analysis of early human neural crest development "The outstanding migration and differentiation capacities of neural crest cells (NCCs) have fascinated scientists since Wilhelm His described this cell population in 1868. Today, after intense research using vertebrate model organisms, we have gained considerable knowledge regarding the origin, migration and differentiation of NCCs. However, our understanding of NCC development in human embryos remains largely uncharacterized, despite the role the neural crest plays in several human pathologies. Here, we report for the first time the expression of a battery of molecular markers before, during, or following NCC migration in human embryos from Carnegie Stages (CS) 12 to 18. Our work demonstrates the expression of Sox9, Sox10 and Pax3 transcription factors in premigratory NCCs, while actively migrating NCCs display the additional transcription factors Pax7 and AP-2alpha. Importantly, while HNK-1 labels few migrating NCCs, p75(NTR) labels a large proportion of this population. However, the broad expression of p75(NTR) - and other markers - beyond the neural crest stresses the need for the identification of additional markers to improve our capacity to investigate human NCC development, and to enable the generation of better diagnostic and therapeutic tools." Cranial neural crest migration: new rules for an old road. "In this review, we discuss recent cellular and molecular discoveries of the CNCC migratory pattern. We focus on events from the time when CNCCs encounter the tissue adjacent to the neural tube and their travel through different microenvironments and into the branchial arches. We describe the patterning of discrete cell migratory streams that emerge from the hindbrain, rhombomere (r) segments r1-r7, and the signals that coordinate directed migration." Derivation of neural crest cells from human pluripotent stem cells. "Here we provide protocols for the step-wise differentiation of human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) into neuroectodermal and NC cells using either the MS5 coculture system or a novel defined culture method based on pharmacological inhibition of bone morphogenetic protein and transforming growth factor-beta signaling pathways." (More? Stem Cells)

Neural crest formation stages and gene regulatory networks.

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, satellite cells, olfactory ensheathing cells
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 Migration

Neural crest cell migration involves an initial epithelial mesenchymal transition to delaminate from the ectoderm layer. Then these neural crest cells, depending upon the rostrocaudal level within the embryo, migrate throughout the embryo with distinct morphological patterns:

• cephalic region - sheet-like mass migration
• trunk - chain migration

See also this recent review.

Human

Human neural crest cell migration (in vitro) A Human neural tube (NT) from an embryo at Carnegie stage 13. B After 16 h, most hNCC have migrated away from the dorsal NT. C The intact NT is detached from the culture dish. D An enriched hNCC population remains, phenotypically similar to murine or avian NCC. E Empirical evaluation of hNCC migration (none to few, some and many) from 31 explanted neural tubes. Third-order polynomial regressions reflect the rostral-to-caudal temporal maturation gradient of the human NT and maturation of NCC. Peaks occur during Carnegie stage 11 at cephalic levels, and during late Carnegie stage 12 at rostral trunk levels (segments extending from somites 5 through the last-formed somite pair).

Chicken

<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.

Movie Source: Original Neural Crest movies kindly provided by Paul Kulesa.

Neural crest migration Chicken Head (movies overview)
‎‎Neural Crest 1 Page | Play	‎‎Neural Crest 2 Page | Play	‎‎Neural Crest 3 Page | Play	‎‎Neural Crest 4 Page | Play	‎‎Neural Crest 5 Page | Play	‎‎Neural Crest 6 Page | Play	‎‎Neural Crest 7 Page | Play

Neural Crest Movies: Migration 01 | Migration 02 | Migration 03 | Migration 04 | Migration 05 | Migration 06 | Migration 07

Textbooks

	Hill, M.A. (2020). UNSW Embryology (20th ed.) Retrieved December 5, 2023, 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
	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
	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: http://www.ncbi.nlm.nih.gov/books/NBK53145/ 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: http://www.ncbi.nlm.nih.gov/books/NBK6098/

Objectives

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.

Neural Crest Structures

Neural Crest Origin Alphabetical list of anatomical structures derived from neural crest. adrenal gland capsule adrenal/interrenal gland alveolar ridge anterior dorsomedial process of autopalatine anterior limiting lamina of cornea anterior process of malleus anterior ramus of pterygoid arachnoid barrier layer basimandibulare body of mandible bony part of hard palate capillary layer of choroid capsular process cardiac valve leaflet cardial valve cartilago ectochoanalis cartilago retronarina choroidal blood vessel corneal epithelium cribriform plate crista interna crista praeopercularis crista subnasalis dentigerous process dorsal root ganglion extremitas anterior footplate of pars media plectri foramen of nasal bone foramen rotundum frontal process of maxilla frontal process of zygomatic bone gonial bone Haller's layer hyaloid canal incisive process of premaxilla inferior part of vestibular ganglion inferior prenasal cartilage interincisive suture interventricular septum membranous part jaw skeleton labial cartilage lamella alaris lamina anterior of pars facialis malleus neck mandibular canal margo orbitalis of pterygoid maxilla ascending process maxillary process of inferior nasal concha maxillary shank Meckel's cartilage meckelian foramen mitral valve anulus nasal septum nasal skeleton orbital fissure otic ligament otic process palatine cartilage palatine process of the pars facialis of the maxilla palatine prong paraganglion (generic) pars facialis of maxillopalatine pars jugalis periodontal ligament piriform aperture planum triangulare posterior ramus of pterygoid prechoanal process premaxilla ascending process processus dorsalis of lamella alaris processus internus of pseudoangular processus lingularis of nasal skeleton processus triangularis of palatoquadrate cartilage quadrate condyle quadrate process of palatoquadrate quadrate ventral process rostral process Sattler's layer secondary palate simian shelf skeletal element of eye region skeleton of upper jaw stratum argenteum of choroid styloid process of temporal bone suboccular arch substantia propria of cornea superior part of vestibular ganglion suprachoroid lamina suture of hard palate sympathetic ganglion tooth of upper jaw tributary of central retinal vein tuberculum sellae uncinate process of ethmoid upper jaw molar epithelium ventral ramus of squamosal ventricular septum intermedium vidian canal vomerine canal zygomatic process of temporal bone Data Origin: Bioportal Uberon is an integrated cross-species anatomy ontology representing a variety of entities classified according to traditional anatomical criteria such as structure, function and developmental lineage.    Links: neural crest | neural crest table | neural crest collapse table | Ectoderm table | Mesoderm table | Endoderm table

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. Hearing - Inner Ear Development

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) Vision - Cornea Development

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

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

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. 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.

Links: Cardiovascular System Development

Development Overview

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

Cranial Neural Crest

Human Eye Neural Crest Timeline

Carnegie Stage	Event
9	an indication of mesencephalic neural crest
10	trigeminal, facial, and postotic components
11	crest-free zones are soon observable in rhombomere 1, 3, and 5
12	rhombomeres 6 and 7 neural crest migrate to pharyngeal arch 3 and then rostrad to the truncus arteriosus
13	nasal crest and the terminalis-vomeronasal complex are last of the cranial crest to appear
9 to 14	otic vesicle primordium descends

Week:	1	2	3	4	5	6	7	8
Carnegie stage:	1 2 3 4	5 6	7 8 9	10 11 12 13	14 15	16 17	18 19	20 21 22 23

Data from a study of 185 serially sectioned staged (Carnegie) human embryos. Links: vision | neural crest | timeline |     Category:Timeline

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 to Stage 23 - 30–35 ganglia

Vagal Neural Crest

• Vagal segment arise at the level of somites 1–7
  • leave neural crest at week 4 and also populate the pharyngeal arches.
  • enter posterior wall of anterior gut, then surround and continue their rostrocaudal migration route
  • migrate into external gut wall just beneath the serosa
  • form an uninterrupted chain of cells that continues migration in the caudal direction
  • mitotically divide during migration
  • differentiate into neurons and glial cells of the myenteric plexus

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

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.

Sacral Neural Crest

• Sacral segment arises caudally to somite 28
  • contributes to the enteric nervous system along the postumbilical gut

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.

Skin Melanocytes

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.

Stimulators

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

Inhibitors

• 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

Historic

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

References

Books

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

Reviews

Erickson AG, Kameneva P & Adameyko I. (2022). The transcriptional portraits of the neural crest at the individual cell level. Semin Cell Dev Biol , , . PMID: 35260294 DOI.

Roth DM, Bayona F, Baddam P & Graf D. (2021). Craniofacial Development: Neural Crest in Molecular Embryology. Head Neck Pathol , 15, 1-15. PMID: 33723764 DOI.

Bhattacharya D, Khan B & Simoes-Costa M. (2021). Neural crest metabolism: At the crossroads of development and disease. Dev Biol , 475, 245-255. PMID: 33548210 DOI.

Leonard CE & Taneyhill LA. (2019). The road best traveled: Neural crest migration upon the extracellular matrix. Semin. Cell Dev. Biol. , , . PMID: 31727473 DOI.

Etchevers HC, Dupin E & Le Douarin NM. (2019). The diverse neural crest: from embryology to human pathology. Development , 146, . PMID: 30858200 DOI.

Szabó A & Mayor R. (2018). Mechanisms of Neural Crest Migration. Annu. Rev. Genet. , 52, 43-63. PMID: 30476447 DOI.

Le Douarin NM & Dupin E. (2018). The "beginnings" of the neural crest. Dev. Biol. , 444 Suppl 1, S3-S13. PMID: 30048640 DOI.

Martik ML & Bronner ME. (2017). Regulatory Logic Underlying Diversification of the Neural Crest. Trends Genet. , 33, 715-727. PMID: 28851604 DOI.

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.

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Articles

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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  Mouse E9.5 neural crest - Crabp1, Sox10, Pax3 PMID 24409333

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  Model neural crest mesenchymal condensation

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  Cardiac Neural Crest Migration

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  Hindbrain neural crest migration

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  Mouse head E9 neural crest GFP

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Cite this page: Hill, M.A. (2023, December 5) Embryology Neural Crest Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_Crest_Development

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G