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Neural Crest Cells and Axonal Specificity Neural Crest ► Where is the neural crest located and why is this region so important? Neural Crest ► What factors are important in the specification of neural crest? Neural Crest ► What are the four domains and their derivatives? cranial ►cartilage, bone, cranial neurons, glia, connective tissue of face trunk ►dorsal root ganglia – sensory neurons, sympathetic ganglia, adrenal medulla, nerves around aorta, melanocytes Neural Crest ► What are the four domains and their derivatives? vagal and sacral ►parasympathetic ganglia of gut cardiac ►melanocytes, neurons, cartilage, connective tissue, wall of large arteries, septum between aorta & pulmonary artery Neural Crest Trunk Neural Crest ► What are the two migration pathways of trunk neural crest cells? Trunk Neural Crest ► What initiates the migration of these cells? transformed from epithelial to mesenchymal cells ►presence of Wnt, FGF, and BMP’s induces formation of Slug and Rho B proteins slug – dissociation of tight junctions, loss of N-cadherin Rho B – promotes actin polymerization into microfilaments Trunk Neural Crest ► How do migratory cells know the route to travel? proteins that promote or impede migration found in extracellular matrix ►promote – fibronectin, laminin, tenascin thrombospondin – found in anterior part of sclerotome ►impede – ephrin proteins found in posterior part of sclerotome stem cell factor promotes proliferation of neural crest that enter skin Trunk Neural Crest ► What cells? is meant by the pluripotency of these ► What determines how a specific cell will differentiate? ► Are all neural crest pluripotent? Cranial Neural Crest ► What is a major distinction between cranial and trunk neural crest? cranial can form bone and cartilage in addition to neurons, melanocytes and glial cells Cranial Neural Crest ► cranial neural crest migrate ventrally from rhombomeres of hindbrain Cranial Neural Crest ► What is involved in intramembranous ossification? Cranial Neural Crest ► What are the cranial placodes? Cranial Neural Crest ► Placodes are induced to form by neighboring tissue Cranial Neural Crest ► What happens during the “second wave” of migration? crest cells migrate dorsally to form glial cells glial cells provide tracks to guide neurons from placodes to hindbrain Cardiac Neural Crest Neuronal Specification ► First decision neuron or epidermis ► Second decision type of neuron ►sensory ►motor ►interneurons ► Third decision target of neuron Neuronal Specification ► What determines the specification of the type of neuron? position of neuronal precursor within neural tube when it forms (birthday) Neuronal Specification ► What determines target of motor neuron? a-p specification ►hox genes from hindbrain through spinal cord and head genes (Otx) in brain regulate in a given region – cell layer ►age of cell – last division ►Lim genes – transcription factors ► Targets are specified before axons extend into periphery Neuronal Specification Pattern Generation ► How does a neuronal axon “know” how to travel to a given area and make specific connections? ► Appears to involve three steps: pathway selection target selection address selection Pattern Generation ► What role does the substrate play in directing the pathway of axons? Pattern Generation ► Are there other molecules known to direct the migration of axons? Pattern Generation ► What is the function of neurotrophins? Pattern Generation ► What is involved in the formation of a synapse? Pattern Generation ► What is the role of neurotropic factors in the survival of neurons? Pattern Generation ► What is known about the migration of retinal ganglion axons? Pattern Generation ► How do axons distinguish between different regions of optic tectum?