neural crest cell
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The neural crest is a ridge-like structure that is formed transiently between the epidermal
ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...
and
neural plate In embryology, the neural plate is a key Development of the human body, developmental structure that serves as the basis for the nervous system. Cranial to the primitive node of the embryonic primitive streak, Ectoderm, ectodermal tissue thickens ...
during
vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, and in turn give rise to a diverse cell lineage—including
melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hea ...
,
craniofacial Craniofacial surgery is a surgical subspecialty that deals with congenital and acquired deformities of the head, skull, face, neck, jaws and associated structures. Although craniofacial treatment often involves manipulation of bone, craniofacial ...
cartilage and bone,
smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
,
dentin Dentin ( ) (American English) or dentine ( or ) (British English) () is a calcified tissue (biology), tissue of the body and, along with tooth enamel, enamel, cementum, and pulp (tooth), pulp, is one of the four major components of teeth. It i ...
,
peripheral A peripheral device, or simply peripheral, is an auxiliary hardware device that a computer uses to transfer information externally. A peripheral is a hardware component that is accessible to and controlled by a computer but is not a core compo ...
and enteric neurons,
adrenal medulla The adrenal medulla () is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecho ...
and
glia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...
. After
gastrulation Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals, the blastocyst, is reorganized into a two-layered or three-layered embryo known as ...
, the neural crest is specified at the border of the
neural plate In embryology, the neural plate is a key Development of the human body, developmental structure that serves as the basis for the nervous system. Cranial to the primitive node of the embryonic primitive streak, Ectoderm, ectodermal tissue thickens ...
and the non-neural
ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...
. During
neurulation Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube. The embryo at this stage is termed the neurula. The process begins when the notochord induces the formati ...
, the borders of the neural plate, also known as the
neural fold The neural fold is a structure that arises during neurulation in the embryonic development of both birds and mammals among other organisms. This structure is associated with primary neurulation, meaning that it forms by the coming together of tis ...
s, converge at the dorsal midline to form the
neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...
. Subsequently, neural crest cells from the roof plate of the neural tube undergo an
epithelial to mesenchymal transition Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of many ...
, delaminating from the neuroepithelium and migrating through the periphery, where they differentiate into varied cell types. The emergence of the neural crest was important in
vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
evolution because many of its structural derivatives are defining features of the vertebrate
clade In biology, a clade (), also known as a Monophyly, monophyletic group or natural group, is a group of organisms that is composed of a common ancestor and all of its descendants. Clades are the fundamental unit of cladistics, a modern approach t ...
. Underlying the development of the neural crest is a
gene regulatory network A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins which, in turn, determine the fu ...
, described as a set of interacting signals,
transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...
, and downstream
effector Effector may refer to: *Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein * ''Effector'' (album), a music album by the Experimental Techno group Download * ''EFFector'', a publication of the El ...
genes, that confer cell characteristics such as multipotency and migratory capabilities. Understanding the molecular mechanisms of neural crest formation is important for our knowledge of human disease because of its contributions to multiple
cell lineage Cell lineage denotes the developmental history of a tissue or organ from the fertilized egg. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses. This starts with the origina ...
s. Abnormalities in neural crest development cause
neurocristopathies Neurocristopathy is a diverse class of pathologies that may arise from defects in the development of tissues containing cells commonly derived from the embryonic neural crest cell lineage. The term was coined by Robert P. Bolande in 1974. After th ...
, which include conditions such as
frontonasal dysplasia Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism (an increased distance between the eyes), a wide nasal root, v ...
,
Waardenburg–Shah syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or one blue eye and one brown eye), a white foreloc ...
, and
DiGeorge syndrome DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent ...
. Defining the mechanisms of neural crest development may reveal key insights into vertebrate evolution and
neurocristopathies Neurocristopathy is a diverse class of pathologies that may arise from defects in the development of tissues containing cells commonly derived from the embryonic neural crest cell lineage. The term was coined by Robert P. Bolande in 1974. After th ...
.


History

The neural crest was first described in the chick embryo by Wilhelm His Sr. in 1868 as "the cord in between" (Zwischenstrang) because of its origin between the neural plate and non-neural ectoderm. He named the tissue "ganglionic crest," since its final destination was each lateral side of the neural tube, where it differentiated into spinal ganglia. During the first half of the 20th century, the majority of research on the neural crest was done using amphibian embryos which was reviewed by Hörstadius (1950) in a well known monograph. Cell labeling techniques advanced research into the neural crest because they allowed researchers to visualize the migration of the tissue throughout the developing embryos. In the 1960s, Weston and Chibon utilized radioisotopic labeling of the nucleus with tritiated thymidine in chick and amphibian embryo respectively. However, this method suffers from drawbacks of stability, since every time the labeled cell divides the signal is diluted. Modern cell labeling techniques such as rhodamine-lysinated dextran and the vital dye diI have also been developed to transiently mark neural crest lineages. The quail-chick marking system, devised by Nicole Le Douarin in 1969, was another instrumental technique used to track neural crest cells. Chimeras, generated through transplantation, enabled researchers to distinguish neural crest cells of one species from the surrounding tissue of another species. With this technique, generations of scientists were able to reliably mark and study the
ontogeny Ontogeny (also ontogenesis) is the origination and development of an organism (both physical and psychological, e.g., moral development), usually from the time of fertilization of the ovum, egg to adult. The term can also be used to refer to t ...
of neural crest cells.


Induction

A molecular cascade of events is involved in establishing the migratory and multipotent characteristics of neural crest cells. This
gene regulatory network A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins which, in turn, determine the fu ...
can be subdivided into the following four sub-networks described below.


Inductive signals

First, extracellular signaling molecules, secreted from the adjacent
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...
and underlying
mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...
such as Wnts, BMPs and Fgfs separate the non-neural
ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...
(epidermis) from the neural plate during neural induction. Wnt signaling has been demonstrated in neural crest induction in several species through gain-of-function and loss-of-function experiments. In coherence with this observation, the promoter region of slug (a neural-crest-specific gene) contains a
binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...
for
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s involved in the activation of Wnt-dependent target genes, suggestive of a direct role of Wnt signaling in neural crest specification. The current role of BMP in neural crest formation is associated with the induction of the neural plate. BMP antagonists diffusing from the ectoderm generates a gradient of BMP activity. In this manner, the neural crest lineage forms from intermediate levels of BMP signaling required for the development of the neural plate (low BMP) and epidermis (high BMP). Fgf from the
paraxial mesoderm Paraxial mesoderm, also known as presomitic or somitic mesoderm, is the area of mesoderm in the neurulating embryo that flanks and forms simultaneously with the neural tube. The cells of this region give rise to somites, blocks of tissue running ...
has been suggested as a source of neural crest inductive signal. Researchers have demonstrated that the expression of dominate-negative Fgf receptor in ectoderm explants blocks neural crest induction when recombined with paraxial mesoderm. The understanding of the role of BMP, Wnt, and Fgf pathways on neural crest specifier expression remains incomplete.


Neural plate border specifiers

Signaling events that establish the neural plate border lead to the expression of a set of transcription factors delineated here as neural plate border specifiers. These molecules include Zic factors, Pax3/7, Dlx5, Msx1/2 which may mediate the influence of Wnts, BMPs, and Fgfs. These genes are expressed broadly at the neural plate border region and precede the expression of bona fide neural crest markers. Experimental evidence places these transcription factors upstream of neural crest specifiers. For example, in ''
Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos'' = strange, πους, ''pous'' = foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described with ...
'' Msx1 is
necessary and sufficient In logic and mathematics, necessity and sufficiency are terms used to describe a material conditional, conditional or implicational relationship between two Statement (logic), statements. For example, in the Conditional sentence, conditional stat ...
for the expression of Slug, Snail, and FoxD3. Furthermore, Pax3 is essential for FoxD3 expression in mouse embryos.


Neural crest specifiers

Following the expression of neural plate border specifiers is a collection of genes including Slug/Snail, FoxD3, Sox10, Sox9, AP-2 and c-Myc. This suite of genes, designated here as neural crest specifiers, are activated in emergent neural crest cells. At least in Xenopus, every neural crest specifier is necessary and/or sufficient for the expression of all other specifiers, demonstrating the existence of extensive cross-regulation. Moreover, this model organism was instrumental in the elucidation of the role of the Hedgehog signaling pathway in the specification of the neural crest, with the transcription factor Gli2 playing a key role. Outside of the tightly regulated network of neural crest specifiers are two other transcription factors Twist and Id. Twist, a bHLH transcription factor, is required for mesenchyme differentiation of the
pharyngeal arch The pharyngeal arches, also known as visceral arches'','' are transient structures seen in the Animal embryonic development, embryonic development of humans and other vertebrates, that are recognisable precursors for many structures. In fish, t ...
structures. Id is a direct target of c-Myc and is known to be important for the maintenance of neural crest stem cells.


Neural crest effector genes

Finally, neural crest specifiers turn on the expression of effector genes, which confer certain properties such as migration and multipotency. Two neural crest effectors, '' Rho GTPases'' and '' cadherins'', function in delamination by regulating cell morphology and adhesive properties. Sox9 and Sox10 regulate neural crest differentiation by activating many cell-type-specific effectors including Mitf, P0, Cx32, Trp and cKit.


Migration

The migration of neural crest cells involves a highly coordinated cascade of events that begins with closure of the
dorsal Dorsal (from Latin ''dorsum'' ‘back’) may refer to: * Dorsal (anatomy), an anatomical term of location referring to the back or upper side of an organism or parts of an organism * Dorsal, positioned on top of an aircraft's fuselage The fus ...
neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...
.


Delamination

After fusion of the
neural fold The neural fold is a structure that arises during neurulation in the embryonic development of both birds and mammals among other organisms. This structure is associated with primary neurulation, meaning that it forms by the coming together of tis ...
s to create the
neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...
, cells originally located in the
neural plate In embryology, the neural plate is a key Development of the human body, developmental structure that serves as the basis for the nervous system. Cranial to the primitive node of the embryonic primitive streak, Ectoderm, ectodermal tissue thickens ...
border become neural crest cells. For migration to begin, neural crest cells must undergo a process called delamination that involves a full or partial
epithelial–mesenchymal transition The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal ...
(EMT). Delamination is defined as the separation of tissue into different populations, in this case neural crest cells separating from the surrounding tissue. Conversely, EMT is a series of events coordinating a change from an
epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
to
mesenchymal Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
. For example, delamination in chick
embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...
s is triggered by a BMP/ Wnt
cascade Cascade, or Cascading may refer to: Science and technology Science * Air shower (physics), a cascade (particle shower) of subatomic particles and ionized nuclei ** Particle shower, a cascade of secondary particles produced as the result of a high ...
that induces the expression of EMT promoting
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s such as SNAI2 and FOXD3. Although all neural crest cells undergo EMT, the timing of delamination occurs at different stages in different organisms: in ''Xenopus laevis'' embryos there is a massive delamination that occurs when the
neural plate In embryology, the neural plate is a key Development of the human body, developmental structure that serves as the basis for the nervous system. Cranial to the primitive node of the embryonic primitive streak, Ectoderm, ectodermal tissue thickens ...
is not entirely fused, whereas delamination in the chick embryo occurs during fusion of the
neural fold The neural fold is a structure that arises during neurulation in the embryonic development of both birds and mammals among other organisms. This structure is associated with primary neurulation, meaning that it forms by the coming together of tis ...
. Prior to delamination, presumptive neural crest cells are initially anchored to neighboring cells by
tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...
proteins such as
occludin Occludin is a transmembrane protein that regulates the permeability of epithelial and endothelial barriers. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with ...
and
cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s such as NCAM and N''-''Cadherin.
Dorsally Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...
expressed BMPs initiate delamination by inducing the expression of the
zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. The term ''zinc finger'' was originally coined to describe the finger-like appearance of a ...
protein transcription factors
snail A snail is a shelled gastropod. The name is most often applied to land snails, terrestrial molluscs, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gas ...
,
slug Slug, or land slug, is a common name for any apparently shell-less Terrestrial mollusc, terrestrial gastropod mollusc. The word ''slug'' is also often used as part of the common name of any gastropod mollusc that has no shell, a very reduced ...
, and twist. These factors play a direct role in inducing the epithelial-mesenchymal transition by reducing expression of
occludin Occludin is a transmembrane protein that regulates the permeability of epithelial and endothelial barriers. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with ...
and N-Cadherin in addition to promoting
modification Modification may refer to: * Modifications of school work for students with special educational needs * Modifications (genetics), changes in appearance arising from changes in the environment * Posttranslational modifications, changes to prote ...
of NCAMs with polysialic acid residues to decrease adhesiveness. Neural crest cells also begin expressing
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
s capable of degrading
cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...
s such as ADAM10 and secreting matrix metalloproteinases (MMPs) that degrade the overlying
basal lamina The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often incorrectly referred to as the basement membrane, though it does constitute a portion of the basement membrane. The b ...
of the neural tube to allow neural crest cells to escape. Additionally, neural crest cells begin expressing
integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s that associate with
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
proteins, including
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
,
fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as col ...
, and
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...
, during migration. Once the basal lamina becomes permeable, neural crest cells can begin migrating throughout the embryo.


Migration

Neural crest cell migration occurs in a
rostral Rostral may refer to: Anatomy * Rostral (anatomical term), situated toward the oral or nasal region * Rostral bone, in ceratopsian dinosaurs * Rostral organ, of certain fish * Rostral scale The rostral scale, or rostral, in snakes and other sca ...
to caudal direction without the need of a neuronal scaffold such as along a
radial glial cell Radial glial cells, or radial glial progenitor cells (RGPs), are Bipolar neuron, bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including as ...
. For this reason the crest cell migration process is termed "free migration". Instead of scaffolding on
progenitor cell A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only diffe ...
s, neural crest migration is the result of repulsive guidance via EphB/ EphrinB and
semaphorin Semaphorins are a class of secreted and membrane proteins that were originally identified as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor (biochemistry), recepto ...
/
neuropilin Neuropilin is a protein receptor active in neurons. There are two forms of Neuropilins, NRP-1 and NRP-2. Neuropilins are transmembrane glycoproteins, first documented to regulate neurogenesis and angiogenesis by complexing with Plexin recep ...
signaling, interactions with the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
, and
contact inhibition In cell biology, contact inhibition refers to two different but closely related phenomena: contact inhibition of locomotion (CIL) and contact inhibition of proliferation (CIP). CIL refers to the avoidance behavior exhibited by fibroblast-like cell ...
with one another. While Ephrin and Eph proteins have the capacity to undergo bi-directional signaling, neural crest cell repulsion employs predominantly forward signaling to initiate a response within the
receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
bearing neural crest cell. Burgeoning neural crest cells express EphB, a
receptor tyrosine kinase Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinas ...
, which binds the EphrinB transmembrane
ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
expressed in the caudal half of each
somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...
. When these two domains interact it causes receptor tyrosine phosphorylation, activation of rhoGTPases, and eventual
cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...
rearrangements within the crest cells inducing them to repel. This phenomenon allows neural crest cells to funnel through the rostral portion of each somite. Semaphorin-neuropilin repulsive signaling works synergistically with EphB signaling to guide neural crest cells down the rostral half of somites in mice. In chick embryos, semaphorin acts in the cephalic region to guide neural crest cells through the
pharyngeal arch The pharyngeal arches, also known as visceral arches'','' are transient structures seen in the Animal embryonic development, embryonic development of humans and other vertebrates, that are recognisable precursors for many structures. In fish, t ...
es. On top of repulsive repulsive signaling, neural crest cells express β1and α4
integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s which allows for binding and guided interaction with
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
,
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...
, and
fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as col ...
of the extracellular matrix as they travel. Additionally, crest cells have intrinsic contact inhibition with one another while freely invading tissues of different origin such as
mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...
. Neural crest cells that migrate through the rostral half of somites differentiate into sensory and sympathetic neurons of the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...
. The other main route neural crest cells take is dorsolaterally between the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...
and the dermamyotome. Cells migrating through this path differentiate into pigment cells of the
dermis The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...
. Further neural crest cell differentiation and specification into their final cell type is biased by their spatiotemporal subjection to morphogenic cues such as BMP, Wnt, FGF, Hox, and Notch.


Clinical significance

Neurocristopathies Neurocristopathy is a diverse class of pathologies that may arise from defects in the development of tissues containing cells commonly derived from the embryonic neural crest cell lineage. The term was coined by Robert P. Bolande in 1974. After th ...
result from the abnormal specification, migration, differentiation or death of neural crest cells throughout embryonic development. This group of diseases comprises a wide spectrum of congenital malformations affecting many newborns. Additionally, they arise because of genetic defects affecting the formation of the neural crest and because of the action of teratogens


Waardenburg syndrome

Waardenburg syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...
is a
neurocristopathy Neurocristopathy is a diverse class of pathologies that may arise from defects in the development of tissues containing cells commonly derived from the embryonic neural crest cell lineage. The term was coined by Robert P. Bolande in 1974. After th ...
that results from defective neural crest cell migration. The condition's main characteristics include piebaldism and
congenital deafness Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spok ...
. In the case of piebaldism, the colorless
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
areas are caused by a total absence of neural crest-derived
pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub ...
-producing
melanocyte Melanocytes are melanin-producing neural-crest, neural crest-derived cell (biology), cells located in the bottom layer (the stratum basale) of the skin's epidermis (skin), epidermis, the middle layer of the eye (the uvea), the inner ear, vagina ...
s. There are four different types of Waardenburg syndrome, each with distinct genetic and physiological features. Types I and II are distinguished based on whether or not family members of the affected individual have
dystopia canthorum Telecanthus, or dystopia canthorum, refers to increased distance between the inner corners of the eyelids (medial canthi), while the inter-pupillary distance is normal. This is in contrast to hypertelorism, in which the distance between the who ...
. Type III gives rise to upper limb abnormalities. Lastly, type IV is also known as Waardenburg-Shah syndrome, and afflicted individuals display both Waardenburg's syndrome and
Hirschsprung's disease Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Most child ...
. Types I and III are inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
fashion, while II and IV exhibit an
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
pattern of inheritance. Overall, Waardenburg's syndrome is rare, with an incidence of ~ 2/100,000 people in the United States. All races and
sex Sex is the biological trait that determines whether a sexually reproducing organism produces male or female gametes. During sexual reproduction, a male and a female gamete fuse to form a zygote, which develops into an offspring that inheri ...
es are equally affected. There is no current cure or treatment for Waardenburg's syndrome.


Hirschsprung's disease

Also implicated in defects related to neural crest cell development and
migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
is
Hirschsprung's disease Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Most child ...
, characterized by a lack of innervation in regions of the
intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
. This lack of
innervation A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...
can lead to further
physiological Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
abnormalities like an enlarged colon (
megacolon Megacolon is an abnormal dilation of the colon (anatomy), colon (also called the large intestine). This leads to hypertrophy of the colon. The dilation is often accompanied by a paralysis of the peristalsis, peristaltic movements of the bowel. In ...
), obstruction of the
bowels The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
, or even slowed growth. In healthy development, neural crest cells migrate into the gut and form the enteric ganglia. Genes playing a role in the healthy migration of these neural crest cells to the gut include RET, GDNF, GFRα, EDN3, and EDNRB. RET, a
receptor tyrosine kinase Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinas ...
(RTK), forms a complex with GDNF and GFRα. EDN3 and EDNRB are then implicated in the same signaling network. When this signaling is disrupted in mice, aganglionosis, or the lack of these enteric ganglia occurs.


Fetal alcohol spectrum disorder

Fetal alcohol spectrum disorder Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person who is exposed to alcohol during gestation. FASD affects 1 in 20 Americans, but is highly misdiagnosed and underdiagnosed. The several forms of the ...
is among the most common causes of developmental defects. Depending on the extent of the exposure and the severity of the resulting abnormalities,
patients A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other healt ...
are diagnosed within a continuum of disorders broadly labeled fetal alcohol spectrum disorder (FASD). Severe FASD can impair neural crest
migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
, as evidenced by characteristic craniofacial abnormalities including short
palpebral fissures The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eyelids. In simple terms, it is the opening between the eyelids. In adult humans, this measures about 10 mm vertically and 30 mm horizontally. Var ...
, an elongated upper lip, and a smoothened
philtrum The philtrum (, from Ancient Greek , lit. 'love charm') or medial cleft is a vertical indentation in the middle area of the upper lip, common to therian mammals, extending in humans from the nasal septum to the tubercle of the upper lip. Toget ...
. However, due to the promiscuous nature of
ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
binding, the mechanisms by which these abnormalities arise is still unclear.
Cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...
explants of neural crest cells as well as
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
developing
zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
embryos An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
exposed to ethanol show a decreased number of migratory cells and decreased distances travelled by migrating neural crest cells. The mechanisms behind these changes are not well understood, but evidence suggests PAE can increase
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
due to increased
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
ic
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
levels caused by IP3-mediated release of calcium from
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
stores. It has also been proposed that the decreased viability of ethanol-exposed neural crest cells is caused by increased
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
. Despite these, and other advances much remains to be discovered about how ethanol affects neural crest development. For example, it appears that ethanol differentially affects certain neural crest cells over others; that is, while craniofacial abnormalities are common in PAE, neural crest-derived pigment cells appear to be minimally affected.


DiGeorge syndrome

DiGeorge syndrome DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent ...
is associated with deletions or translocations of a small segment in the
human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
chromosome 22 Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 51 million DNA base pairs and representing b ...
. This deletion may disrupt rostral neural crest
cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryogenesis, embryonic development, wound healing and immune system, immune responses all require the orchestrated movemen ...
or
development Development or developing may refer to: Arts *Development (music), the process by which thematic material is reshaped * Photographic development *Filmmaking, development phase, including finance and budgeting * Development hell, when a proje ...
. Some defects observed are linked to the pharyngeal pouch system, which receives contribution from rostral migratory crest cells. The
symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
of DiGeorge syndrome include congenital heart defects, facial defects, and some
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
and
learning disabilities Learning disability, learning disorder, or learning difficulty (British English) is a condition in the brain that causes difficulties comprehending or processing information and can be caused by several different factors. Given the "difficulty ...
. Patients with 22q11 deletions have also been reported to have higher incidence of
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
and
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
.


Treacher Collins syndrome

Treacher Collins syndrome Treacher Collins syndrome (TCS) is a genetic disorder characterized by deformities of the ears, eyes, cheekbones, and chin. The degree to which a person is affected, however, may vary from mild to severe. Complications may include breathing pr ...
(TCS) results from the compromised development of the first and second
pharyngeal arches The pharyngeal arches, also known as visceral arches'','' are transient structures seen in the Animal embryonic development, embryonic development of humans and other vertebrates, that are recognisable precursors for many structures. In fish, t ...
during the early embryonic stage, which ultimately leads to mid and lower face abnormalities. TCS is caused by the
missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn alt ...
of the TCOF1 gene, which causes neural crest cells to undergo
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
during
embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...
. Although
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
of the TCOF1 gene are among the best characterized in their role in TCS, mutations in POLR1C and POLR1D
genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
have also been linked to the
pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...
of TCS.


Cell lineages

Neural crest cells originating from different positions along the
anterior Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
-posterior axis develop into various tissues. These regions of the neural crest can be divided into four main functional domains, which include the cranial neural crest, trunk neural crest, vagal and sacral neural crest, and cardiac neural crest.


Cranial neural crest

The cranial neural crest migrates dorsolaterally to form the craniofacial mesenchyme that differentiates into various cranial ganglia and craniofacial cartilages and bones.Taneyhill, L.A. (2008). "To adhere or not to adhere: the role of Cadherins in neural crest development". Cell Adh Migr. 2, 223–30. These cells enter the pharyngeal pouches and arches where they contribute to the
thymus The thymus (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...
, bones of the middle ear and jaw and the
odontoblasts In vertebrates, an odontoblast is a Cell (biology), cell of neural crest origin that is part of the outer surface of the pulp (tooth), dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance be ...
of the tooth primordia.


Trunk neural crest

The trunk neural crest gives rise to two populations of cells. One group of cells fated to become
melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hea ...
migrates dorsolaterally into the ectoderm towards the ventral midline. A second group of cells migrates ventrolaterally through the anterior portion of each
sclerotome The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...
. The cells that stay in the sclerotome form the
dorsal root ganglia A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dors ...
, whereas those that continue more ventrally form the sympathetic ganglia,
adrenal medulla The adrenal medulla () is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecho ...
, and the nerves surrounding the aorta.


Vagal and sacral neural crest

Vagal and sacral neural crest cells develop into the ganglia of the
enteric nervous system The enteric nervous system (ENS) is one of the three divisions of the autonomic nervous system (ANS), the others being the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). It consists of a mesh-like system of neurons th ...
and the parasympathetic ganglia.


Cardiac neural crest

Cardiac neural crest Neural crest cells are multipotent cells required for the development of cells, tissues and organ systems. A subpopulation of neural crest cells are the cardiac neural crest complex. This complex refers to the cells found amongst the midotic placo ...
develops into melanocytes, cartilage, connective tissue and neurons of some pharyngeal arches. Also, this domain gives rise to regions of the heart such as the musculo-connective tissue of the large arteries, and part of the
septum In biology, a septum (Latin language, Latin for ''something that encloses''; septa) is a wall, dividing a Body cavity, cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Hum ...
, which divides the pulmonary circulation from the aorta. The semilunar valves of the heart are associated with neural crest cells according to new research.


Evolution

Several structures that distinguish the vertebrates from other chordates are formed from the derivatives of neural crest cells. In their "New head" theory, Gans and Northcut argue that the presence of neural crest was the basis for vertebrate specific features, such as sensory ganglia and cranial skeleton. Furthermore, the appearance of these features was pivotal in vertebrate evolution because it enabled a predatory lifestyle. However, considering the neural crest a vertebrate innovation does not mean that it arose '' de novo''. Instead, new structures often arise through modification of existing developmental regulatory programs. For example, regulatory programs may be changed by the
co-option Co-option, also known as co-optation and sometimes spelt cooption or cooptation, is a term with three common meanings. It may refer to: 1) The process of adding members to an elite Social group, group at the discretion of members of the body, us ...
of new upstream regulators or by the employment of new downstream gene targets, thus placing existing networks in a novel context. This idea is supported by
in situ hybridization ''In situ'' hybridization (ISH) is a type of Hybridisation (molecular biology), hybridization that uses a labeled complementary DNA, RNA or modified nucleic acid strand (i.e., a Hybridization probe, probe) to localize a specific DNA or RNA seq ...
data that shows the conservation of the neural plate border specifiers in protochordates, which suggest that part of the neural crest precursor network was present in a common ancestor to the chordates. In some non-vertebrate chordates such as tunicates a lineage of cells (melanocytes) has been identified, which are similar to neural crest cells in vertebrates. This implies that a rudimentary neural crest existed in a
common ancestor Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. According to modern evolutionary biology, all living beings could be descendants of a unique ancestor commonl ...
of vertebrates and tunicates.


Neural crest derivatives

Ectomesenchyme (also known as mesectoderm):
odontoblasts In vertebrates, an odontoblast is a Cell (biology), cell of neural crest origin that is part of the outer surface of the pulp (tooth), dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance be ...
, dental papillae, the chondrocranium ( nasal capsule,
Meckel's cartilage In humans, the cartilaginous bar of the mandibular arch is formed by what are known as Meckel's cartilages (right and left; also known as Meckelian cartilages), above which the incus and malleus are located. Meckel's cartilage arises from the fir ...
, scleral ossicles, quadrate, articular, hyoid and columella),
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
l and laryngeal cartilage, the
dermatocranium The dermatocranium is the portion of the cranium that is composed of dermal bone, as opposed to the endocranium and splanchnocranium, which are composed of endochondral bone. The dermatocranium comprises the skull roof, the facial skeleton (usu ...
(membranous bones), dorsal fins and the turtle plastron (lower vertebrates), pericytes and smooth muscle of branchial arteries and veins,
tendons A tendon or sinew is a tough band of dense fibrous connective tissue that connects muscle to bone. It sends the mechanical forces of muscle contraction to the skeletal system, while withstanding tension. Tendons, like ligaments, are made of ...
of ocular and masticatory muscles,
connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
of head and neck glands (pituitary, salivary, lachrymal, thymus, thyroid)
dermis The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...
and adipose tissue of calvaria, ventral neck and face Endocrine cells:
chromaffin cell Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the adrenal medulla, medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to ...
s of the adrenal medulla, glomus cells type I/II. Peripheral nervous system:
Sensory neuron Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potentials. This process is called sensory transduc ...
s and glia of the
dorsal root ganglia A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dors ...
, cephalic ganglia (VII and in part, V, IX, and X), Rohon-Beard cells, some
Merkel cell Merkel cells, also known as Merkel–Ranvier cells or tactile epithelial cells, are oval-shaped mechanoreceptors essential for light touch sensation and found in the skin of vertebrates. They are abundant in highly sensitive skin like that of th ...
s in the whisker,
Satellite glial cell Satellite glial cells, formerly called amphicytes, are glial cells that cover the surface of neuron cell bodies in ganglia of the peripheral nervous system. Thus, they are found in sensory, sympathetic, and parasympathetic ganglia. Both sat ...
s of all autonomic and sensory ganglia, Schwann cells of all peripheral nerves. Enteric cells: Enterochromaffin cells.
Melanocyte Melanocytes are melanin-producing neural-crest, neural crest-derived cell (biology), cells located in the bottom layer (the stratum basale) of the skin's epidermis (skin), epidermis, the middle layer of the eye (the uvea), the inner ear, vagina ...
s, iris muscle and pigment cells, and even associated with some tumors (such as melanotic neuroectodermal tumor of infancy).


See also

* First arch syndrome * DGCR2—may control neural crest cell migration *
List of human cell types derived from the germ layers This is a list of Cell (biology), cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte (human), Trichocyte * Keratinocyte Anterior pi ...


References


External links

* *
Diagram
at
University of Michigan The University of Michigan (U-M, U of M, or Michigan) is a public university, public research university in Ann Arbor, Michigan, United States. Founded in 1817, it is the oldest institution of higher education in the state. The University of Mi ...

Hox domains in chicks
{{Authority control Embryology of nervous system Ectoderm Chordate anatomy Animal nervous system