NEURAL CREST

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BY DR NEETA CHHABRA 30 JANUARY ‘10

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A band of cells at the outermost edges of neural plate lying between the neural tube and ectoderm of an embryo during neural tube formation. Fourth germ layer & Ectomesenchyme . Present only in Vertebrates. Migrate during or shortly after neurulation .

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WilhelmHis , Swiss Embryologist in 1868. Zwischenstrand - the intermediate cord . Also known as Ganglion Crest. The term neural crest was first used by Arthur Milnes Marshall 1879.

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NEURULATION

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Induced by Notochord. Bmp-4 and 7 (Bone Morphogenetic Protein). Chordin, Noggin and Follistatin inhibit Bmp-4 causing the overlying cells of the ectoderm to develop into neural cells. Wnt-3a and FGF (Fibroblast growth factor).

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Cells become high columnar Median Hinge Point (MHP)

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Formation of Dorso Lateral Hinge Point (DLHP)

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Cells located at the very edges of lateral plates of the folding neural tube separate and migrate to become a variety of diff cells.

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failure to close = anencephaly failure to close = spina bifida Anterior neural pore Posterior neural pore

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Neural crest cells migrate and differentiate into a wide variety of adult structures. Migrations begin cranially and gradually extend caudally. Determined by intrinsic properties of the neural crest cells and the features of the external environment. Pharyngeal arch Migrating neural crest cells Neural Folds

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Bartelmey and Holmdahl 1920 Ablation Vital dyes Experimentation Johnston 1960 Radio isotope labelling of cells Weston 1963 Labelling with lipophilic dye ( dil ) LE Douarin 1969 Quail chick neural crest transfer

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EXTRA CELLULAR MATRIX Permissive Substrates Hyaluronic acid Plasminogen Activator Fibronectin , Laminin , Tenascin , Collagen Thrombospondin Inhibitors Organised Basal Laminae Ephrin proteins Chondroitin Sulphate Chemotactic & maintenance factors

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Nichols, 1987. Neural crest cells elongate and their organelles migrate closer to the basal region of the epithelium. Cell to cell contact is lost and the cells begin to take on mesenchymal characteristics. The basal cells release processes that penetrate the basal lamina that in effect degrades allowing the basal cells to finally break free and become mesenchymal . The apical cells then form a new basal lamina.

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Epithelial to mesenchymal transformation Slug (transcription factor) RhoB Protein Changes in adhesion N-Cam, N- Cadherin and E- Cadherin , are down regulated Integrin Hyaluronic acid Motility Genetic Envt triggers

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Neural crest cells migrate along ECM through a definite route. Two mechanisms : Contact inhibition Contact guidance

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Reversal of the mechanisms . Adhesion changes. N-CAM, N- cadherin and E- cadherin re-expressed. Integrins are down regulated. Decline hyaluronic acid levels. Fibronectin decreased.

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Due to the difference in migratory pathways and derivatives, neural crest population has been divided into following main functional but overlapping groups :- Cranial Cardiac Vagal Trunk Lumbosacral

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Extends from diencephalon to 6 th somite . Migrate before the closure of neural tube. Dorsolaterally into the branchial arches and the face to form the bones, cartilage, nerves and connective tissue. It also produces pigment and cranial nerves.

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Caudal Forebrain Midbrain Rostral Hindbrain Caudal Hindbrain Each population has different patterns of migration and derivaties

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At caudal forebrain and midbrain level Migrate as a broad unsegmented sheet :- Periocular Skeleton Connective Tissue of Eye Membrane Bones of Face Ciliary , Trigeminal Ganglion Schwann Cells

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At the Hind brain level Segmented into 8 rhombomeres . Migrate in a segmental fashion. 3 broad sheets :- From r1 and r2 into 1 st arch From r4 into 2 nd arch From r6 into 3 rd , 4 th arches

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Bones and connective tissue of face Thymus Parafollicular cells of thyroid Parathyroid gland Odontoblasts of teeth Sensory ganglia of 5 th , 7 th , 9 th , 10 th cranial nerves Schwann cells Into optic vesicle - cornea, sclera, ciliaris muscle

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Extends from rhombomere 7 to the third somite . Already determined to generate cardiac cells and other regions of neural crest cannot substitute for it. Cells migrate into :- 3 rd , 4 th , 6 th , pharyngeal arches To the heart

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Melanocytes , neurons, cartilage and connective tissue of 3 rd , 4 th & 6 th pharyngeal arches. Musculoconnective tissue wall of large arteries. Septum that separates pulmonary circulation from aorta.

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Lies between vagal and sacral neural crest. Extends from somite 6 through the tail. Cells migrate after closure of neural tube. Does not give rise to bone and cartilage.

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Three routes Ventral pathways Dorsolateral pathways Rostrocaudal axis along the Aorta

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Dorsal root ganglia remain at the same rostro -caudal level. Sympathetic ganglion migrate two or three somite lengths rostrally and caudally. Melanocytes migrate long distances along the embryo's axis.

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Dorsal root ganglia Sympathetic chain ganglia Chromaffin cells of Adrenal medulla Pre Aortic Ganglia Melanocytes Pia and Arachnoid of Spinal Cord Schwann Cells

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Vagal neural crest - Near somites 1-7 Sacral neural crest - Posterior to somite 28 Form the parasympathetic ganglia of the gut

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Neural derivatives Mesenchymal derivatives

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Sensory neurons of Cranial Nerve Ganglia Sensory neurons of Dorsal Nerve Root Ganglia Satellite cells in all Sensory Ganglia Sympathetic Ganglia and Plexuses Parasympathetic Ganglia and Plexuses Schwann cells of all Peripheral nerves C cells of Thyroid Chromaffin cells of Adrenal Medulla Melanocytes Enteric Plexuses

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Connective tissue and bones of face and neck Choroid and sclera of eye Dentine of teeth Connective tissue of thyroid, parathydroid gland and thymus Connective tissue of lacrimal,nasal,oral and salivary glands Conotruncal septum in the heart Tunica media of outflow tract of heart and great blood vessels Arachnoid and piamater

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Single neural crest cell can differentiate into any of several different cell types. Parasympathetic neurons produce acetylcholine. Sympathetic neurons produce norepinephrine . Vagal and thoracic neural crests are reciprocally transplanted. Comparable to stem cell.

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Defects of neural crest development Pathologies assoc with neural crest derivatives Two major categories : Tumors of neural crest Defects of migration

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Pheochromocytoma Neuroblastoma Medullary carcinoma of the thyroid Carcinoid tumors Neurofibromatosis Melanoma

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Hirshsprung's disease Aorticopulmonary septation defect of heart Cleft Lip, cleft palate. Frontonasal dysplasia Waardenburg Type I and II and Albinism Mandibulofacial dysostosis - underdevelopment of 1 st arch Robin sequence : Triad of Micrognathia Cleft palate Glossoptosis

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Di George syndrome Triad of Malformations Minor Craniofacial defects Total or partial agenesis of derivatives of 3 rd 4 th ,6 th arches Cardiovascular anomalies

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CATCH-22 : C ardiac defects A bnormal face T hymic hypoplasia C left palate H ypocalcemia Deletions of chromosome 22 Charge Association : C oloboma of Eye H eart defects A tresia of Choanae R etarded growth and development G enital and Urinary anomalies E ar anomalies and Hearing loss

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THANK YOU