Neural crest

By : Sara Abd El Hafiz Mehrez

origin The neural crest (NC) is ectodermal in origin,

They have an amazing differentiation potential to generate both ectodermal and mesodermal derivatives. Also have a migration potential that involves them in the embryogenesis of many distant tissues

Derived from the neural folds on both sides of the neural groove that runs longitudinally along the axis of the embryo and deepens progressively to close the neural tube. Cells located on either side of the tube are the first elements of the NC that will subsequently adopt a segmental pattern .

Neural crest formation

•Germ cells layers

Cell lineages Cranial neural crest

migrates dorsolaterally to form the craniofacial mesenchyme that differentiates into various cranial ganglia and craniofacial cartilages and bones . These cells enter the pharyngeal pouches and arches where they contribute to the thymus, bones of the middle ear and jaw and the odontoblasts of the tooth primordia. Vagal and sacral neural crest develop into the ganglia of the enteric nervous system and the parasympathetic ganglia

Trunk neural crest Gives rise to two populations of cells. One group of cells fated to become melanocytes migrates dorsolaterally into the ectoderm towards the ventral midline. A second group of cells migrates ventrolaterally through the anterior portion of each sclerotome. The cells that stay in the sclerotome form the dorsal root ganglia, whereas those that continue more ventrally form the sympathetic ganglia, adrenal medulla, and the nerves surrounding the aorta Cardiac neural crestDevelops 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, which divides the pulmonary circulation from the aorta. The semilunar valves of the heart are associated with neural crest cells according to new research

Neural Crest derivatives

• Mesectoderm : odontoblasts, dental papillae, the chondrocranium (nasal capsule, Meckel's cartilage, scleral ossicles, quadrate, articular, hyoid and columella), tracheal and laryngeal cartilage, the dermatocranium (membranous bones), dorsal fins and the turtle plastron (lower vertebrates), pericytes and smooth muscle of branchial arteries and veins, tendons of ocular and masticatory muscles, connective tissue of head and neck glands (pituitary, salivary, lachrymal, thymus, thyroid) dermis and adipose tissue of calvaria, ventral neck and face

• Endocrine Cells: chromaffin cells of the adrenal medulla, parafollicular cells of the thyroid, glomus cells type I/II

• Peripheral nervous system: Sensory neurons and glia of the dorsal root ganglia, cephalic ganglia (VII and in part, V, IX, and X), Rohon-Beard cells, some Merkel cells in the whisker,Satellite glial cells of all autonomic and sensory ganglia, Schwann cells of all peripheral nerves

• Melanocytes and iris pigment cells

Malformations of NC origin

• Facial clefts, ear malformations, and other

Facial defects• Branchial fistulae and anomalies of pharyngeal arch derivatives• Cardiovascular malformations• Pigmentary disorders• Abnormal enteric innervation• Tumors• Hemangiomas and vascular

malformations

Facial clefts, ear malformations, and otherfacial defects

The advancement of the embryonal frontonasal bud and

the fusion of its lateral and medial processes give rise to the nose and upper lip. The maxillary processes fuse laterally with these structures to shape the upper face. Below the future mouth, the mandibular processes fuse in the midline to form the jaw. Components of the first and second arches

form the auricle. The shaping of the face is therefore

patterned under the influence of the NC. The more common malformations of the

region, like preauricular tags, microtia, cleft lip, and cleft palate as well as other more complex facial anomalies like CHARGE association, Treacher Collins, or Goldenhar syndromes are NC-related

Branchial fistulae and anomalies of pharyngeal

arch derivatives Brachial fistula and cyst due to persistant 2nd

pharyngeal arch which normally regress

Malformations of the endocrine glands that are derived from the pharyngeal arches and pouches have the same origin :

The paired thymus anlage, which originate from the third pharyngeal pouch on each side

The parathyroids, derived from the third (lower glands) and fourth pharyngeal pouches (upper glands)

C-cells of the thyroid (derived from the ultimobranchial body in the fifth pouch)

Brachial cyst

Cardiovascular malformations During the embryonal period the initially tubular

heartfolds itself to acquire an S-shape that outlines the final design of the atria and the ventricles. The outflow tract that corresponds to the end of the tube will be ultimately cleaved to form separate aorta and pulmonary arteries. Part of the cellular material involved in this cleavage of NC origin . TA, DORV, Tetralogy of Fallot (TOF), narrowoutflow pulmonary tract (NOPT), transposition of the greatvessels, perimembranous ventricular septal defect (VSD),and other heart defects are the result of defective NCinfluence on the region .

Pigmentary disorders Albinism is the result of the absence of this

migration/differentiation congenital nevi . Neurocutaneous melanoses with their

malignant potential neurofibromatosis of Von Recklinghausen in which there are cafe´-au-lait cutaneous spots, neurofibromas, skeletal deformities and a potential for several varieties of tumors is also the result of NC dysfunction .

Tuberous sclerosis and all the gastrointestinal polyposes in which there are mucosal or cutaneous pigmentary spots (Peutz Jeghers, Cowden, Cronkhite-Canada etc) have oncogenic potential and share their NC-related origin .

neurofibromatosis albinism

Abnormal enteric innervation

Hirschsprung disease related to mutations of the RET protooncogene

Neuronal intestinal dysplasia is also of NC origin and has been studied in animals with mutations of the gene Ncx/Hox11L.1

Waardenburg syndrome, there is abnormal pigmentation of the hair, skin, and irises facial dysmorphia; neurosensorial deafness; and sometimes hypo- or aganglionosis that is related to mutations of SOX10 or Pax3 genes . The same condition is observed in some animal strains with mutations of these genes

Tumors Due to abnormal proliferation of NC

cells . Neuroblastoma , Neuroblastoma ,

ganglioneuroma are good examples of the differentiation potential of these cells

Peripheral neuroectodermal tumor, known as Askin tumor when it is located in the thoracic wall, is probably derived from the Schwann cells of the intercostal nerve that are NC-derived

Hemangiomas and vascular malformations

The concept that hemangiomas and vascular malformations are derived from the NC is relatively new, but accepted.

The flat vascular malformations that are located in the areas corresponding to the cutaneous innervation of the cranial nerves may have intracraneal extension (Sturge-

Weber syndrome) and are of this origin .

References

[1 ]Moore KL, Persaud TVN. The developing human. Clinically oriented embryology. 7th ed. Philadelphia7 Saunders; 2003. p. 560.

[2 ]Larsen WJ. Human embryology. 2nd ed. New York7 Churchill Livingstone; 1997. p. 512

[3 ]Johnston MC, Bronsky PT. Animal models for human craniofacial malformations. J Craniofac Genet Dev Biol 1991;11:277 - 91.

[4 ]Granstrom G, Kullaa-Mikkonen A. Experimental craniofacialmalformations induced by retinoids and resembling branchial arch syndromes. Scand J Plast Reconstr Surg Hand Surg 1990;24:3 - 12.