Neural Crest Cells and Axonal Specificity

1. Neural Crest Cells and Axonal Specificity

2. Neural Crest • Where is the neural crest located and why is this region so important?

3. Neural Crest • What factors are important in the specification of neural crest?

4. 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

5. 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

6. Neural Crest

7. Trunk Neural Crest • What are the two migration pathways of trunk neural crest cells?

8. 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

9. 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

10. Trunk Neural Crest • What is meant by the pluripotency of these cells? • What determines how a specific cell will differentiate? • Are all neural crest pluripotent?

11. 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

12. Cranial Neural Crest • cranial neural crest migrate ventrally from rhombomeres of hindbrain

13. Cranial Neural Crest • What is involved in intramembranous ossification?

14. Cranial Neural Crest • What are the cranial placodes?

15. Cranial Neural Crest • Placodes are induced to form by neighboring tissue

16. 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

17. Cardiac Neural Crest

18. Neuronal Specification • First decision • neuron or epidermis • Second decision • type of neuron • sensory • motor • interneurons • Third decision • target of neuron

19. Neuronal Specification • What determines the specification of the type of neuron? • position of neuronal precursor within neural tube • when it forms (birthday)

20. 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

21. Neuronal Specification

22. 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

23. Pattern Generation • What role does the substrate play in directing the pathway of axons?

24. Pattern Generation • Are there other molecules known to direct the migration of axons?

25. Pattern Generation • What is the function of neurotrophins?

26. Pattern Generation • What is involved in the formation of a synapse?

27. Pattern Generation • What is the role of neurotropic factors in the survival of neurons?

28. Pattern Generation • What is known about the migration of retinal ganglion axons?

29. Pattern Generation • How do axons distinguish between different regions of optic tectum?