Page 1Page 2Page 3Page 4Page 5Page 6Biology 4361Developmental BiologyGilbert Chapter 13. Neural Crest Cells and Axonal SpecificityDecember 7, 2006THE NEURAL CREST - although derived from ectoderm, neural crest could be considered the “fourth germ layer” - NC cell form: - neurons and glial cells of the sensory, sympathetic, parasympathetic nervous systems- epinephrine producing cells of the adrenal gland- pigment containing cells of the epidermis- many of the skeletal and connective tissue components of the head - fate of individual neural crest cells depends to a large degree on the locations to which theymigrateSpecification of the Neural Crest CellsNeural crest cells originate at the dorsal-most region of the neural tube - neural plate border specified by an intermediate concentration of BMPsRegionalization of the neural crest (summary) - neural crest is a transient structure; cells disperse soon after the neural tube closes - can be divided into four main, overlapping regions; each with characteristic derivatives andfunctions- Cranial (cephalic) neural crest cells; migrate dorsolaterally to form- craniofacial mesenchyme; differentiates into:- cartilage, bone, cranial neurons, glia, and connective tissues of theface- enter pharyngeal arches and pouches; give rise to:- thymic cells, odontoblasts of the tooth primordia, bones of themiddle ear and jaw- Trunk neural crest cells; - early migrating cells migrate ventrolaterally through anterior half of eachsomitic sclerotome (blocks of mesodermal cells that differentiate intovertebral cartilage of spine)- those trunk NC cells that remain in the sclerotomes become the dorsalroot ganglia containing the sensory neurons- those that locate more ventrally form the sympathetic ganglia, adrenalmedulla, and the nerve clusters surrounding the aorta- later migrating trunk NC cells migrate dorsolaterally into the ectoderm; becomemelanocytes - Vagal and sacral neural crest cells - generate the parasympathetic (enteric) gangliaof the gut- Cardiac neural crest (subregion of the vagal neural crest; extends from the 1 to 3st rdsomites); can develop into:- melanocytes, neurons, cartilage, connective tissues- all form parts of the 3 , 4 , 6 pharyngeal archesrd th th- also produces the entire muscular-connective tissue wall of the large arteries(outflow tracts) arising from the heart; contributes to the septum thatseparates pulmonary circulation from the aorta (truncus arteriosus)Trunk Neural CrestMigration pathways of trunk neural crest cellsTwo major pathways taken by migrating trunk neural crest cells - ventral pathway - earliest migrating- these cells become the sensory (dorsal root) and sympathetic neurons, adrenomedullarycells, Schwann cells- in mammals and birds (not fish or frogs), these cells migrate ventrally through theanterior section of the sclerotome only- NC cells located opposite the posterior portions of the sclerotome first migrateanteriorly along the neural tube, then enter anterior sclerotome - dorsolateral pathway - later migrating- travel between epidermis and dermis- enter ectoderm through holes in the basal lamina- become melanocytes- colonize skin and hair folliclesThe mechanisms of trunk neural crest migrationEmigration from the Neural Tube - central questions: - what signals initiate migration?- when does the migratory agent become competent to respond to these signals?- how do the migratory agents know the route to travel?- what signals indicate that the destination has been reached? - migration initiation occurs through interactions of the neural plate with the presumptiveepidermis- NC cells are originally epithelial, so first, epithelia - mesenchymal transformation- stimulated by Wnts or BMP4, 7- cells produce Slug and RhoB- “pushes and pulls” are necessary (to allow cells to leave the NC)- RhoB - promotes actin polymerization into microfilaments and attachment ofmicrofilaments to cell membrane- Slug - activates factors that dissociate E-cadherins binding cells togetherThe Ventral Migration Pathway - migration is initiated and controlled by the maturation of the somites adjacent to the neural tube- first part of the somite to mature is the sclerotome (forms the vertebral cartilage)- first migrating NC cells enter the ventral pathway through the anterior portion of eachsclerotome- other NC cells remain above the neural tube (the staging area) - the migration pathway is controlled by extracellular matrices and by chemotactic factorsthe cell encounter- one set of ECM proteins is permissive: fibronectin, laminin, tenascin, collagens, andproteoglycans- also, migrating trunk NC cells express integrin protein, which binds several ECMproteins- integrin expression is necessary for locomotion and survival of NC cells- lacking integrin, cells become disoriented and undergo apoptosis- also express thrombospondin (ECM molecule); found in the anterior, not posteriorsclerotome- substrate for NC cell adhesion and migration- posterior sclerotome inhibits NC cell migration:- ephrins and semaphorin-3F expressed in posterior- NC cells avoid area- set up segmentation pattern of peripheral nervous system- soluble factors also control migration of particular populations of NC cells- e.g. glial-derived neurotrophic factor (GDNF) produced by the gut mesenchyme- attract NC cells from vagal and sacral regions - these form the enteric ganglia of the colon and control intestinalperistalsis- adrenal gland formation: adrenal gland contains two cell populations: - outer (cortex) secrete hormones such as cortisol- derived from intermediate mesoderm- inner (medulla) secretes hormones such as epinephrine- derived from trunk NC- directed to medulla-forming region by chemotactic factors arisingform the mesoderm forming the cortex- BMP gradientThe Dorsal Migration Pathway - the latest parts of the somite to mature are the dermatomes - form the dermis of the back- NC cells migrate in the dorsal pathway only after dermatome maturation- dermis cells secrete chemotactic factors that attract NC cells - dorsal NC cells become melanocytes- ECM creates a positive guide for dorsal NC cell migration (note - ECM played permissiveand negative roles in ventral trunk NC cell migration)- ephrins expressed along the dorsolateral migration pathway stimulates the migration oflate-migrating cells - NC cells migrating along the dorsal route become committed to forming melanocytes- they travel through dermis and