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 is meant by the pluripotency of these cells? ► 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? pathway of axons?

Pattern Generation ► Are there other molecules known to direct the migration of axons? 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?