upcoming sessions april 22:nervous system development lecture april 24:reviews of axonal pathfinding...
TRANSCRIPT
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Upcoming Sessions
April 22: Nervous System Development Lecture
April 24: Reviews of Axonal Pathfinding in Sensory Systems
April 29: Inner Ear Development LectureMay 1: Auditory System Pathfinding
Research PapersMay 6: Reviews of Organ of Corti
DifferentiationMay 8: Hair Cell Differentiation Research
Papers
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Inner ear developmentNervous system development
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Nervous System Development
• Formation and differentiation of the neural tube
• Tissue architecture of the central nervous system
• Differentiation of neurons/generation of neural diversity
• Pattern generation in the nervous system
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Chick Embryo Whole Mounts
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Primary Neurulation(formation of neural tube)
MHP=medial hinge point
Neural groove
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Primary Neurulation (cont’d)
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Primary Neurulation (cont’d)3 steps:
1. Formation of the neural plate• Underlying dorsal mesoderm signals ectodermal cells
to elongate and form the neural plate (columnar cells)2. Bending of the neural plate
• MHP cells become anchored to the notochord and change shape forcing formation of the neural groove
• DLHP cells become anchored to the surface ectoderm3. Closure of the neural tube
• Folds adhere to each other and cells merge• In mammals, cranial neural crest cells migrate to the
folds; spinal NC cells don’t migrate until after closure• Neural tube don’t close simultaneously (3 sites in
mammals): anterior neuropore closes first• Separation from surface ectoderm occurs when neural
tube cells switch from expressing E-cadherin (like ectoderm) to N-cadherin and N-CAM
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Secondary Neurulation
• Mesenchyme cells coalesce into a solid cord that subsequently forms cavities that combine to form the hollow tube
• Separately formed tubes join together
• Occurs at transition regions at the junctions of tubes formed via primary neurulation
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Nervous System Development
• Formation and differentiation of the neural tube
• Tissue architecture of the central nervous system
• Differentiation of neurons/generation of neural diversity
• Pattern generation in the nervous system
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Human Brain Development
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Neural Stem Cells andthe Location of Dividing Cells
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Cell Migration
After their terminal division, cells migrate from the lumen toward the surface
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Lamination
Cells with the earliest birthdays migrate the shortest distances
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Adult Stem Cells
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Nervous System Development
• Formation and differentiation of the neural tube
• Tissue architecture of the central nervous system
• Differentiation of neurons/generation of neural diversity
• Pattern generation in the nervous system
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Generation of neurons
• Neural stem cells can become:1. Ventricular (ependymal) cells: make CSF2. Neurons: generate and conduct electrical
potentials3. Glial cells: provide structure, insulate axons
• Numbers are staggering:o 1011 neurons associated with 1012 gliao Each neuron forms as many as 100,000
synapses with 1,000 to 1,000,000 other neurons
o Neurons can be separated from their targets by distances of meters
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Cell fate
• Neural vs. glial vs. epidermal fate is determined by the Notch-Delta pathwayo Inducing proteins are bound to the cell surfaceo Cells expressing Delta, Jagged or Serrate
proteins activate adjacent cells that express the Notch protein by causing a conformational change that causes Presinilin-1 to cleave part of the Notch intracellular domain
o Cleaved portion of Notch goes to the nucleus and activates transcription factors
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Neuronal type
• Determined initially by dorsal/ventral position within the neural tube, which is established by birthdate
• Gradients of paracrine factors then cause differential gene expression which determines type (e.g., motor vs. sensory)
• Early-born neurons can secrete retinoid signals that alter gene expression of later-born neurons as they migrate through to their final position
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Dorsal/ventral Specification
• Eventually, in spinal cord dorsal=sensory ventral=motor
• Ventral is specified by notocord, via Sonic hedgehog (Shh) converts MHC to become floor plate more Shh
• Dorsal by ectoderm via TGF-β roof plate more TGF-β
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Paracrine Factor Gradients
Motor neurons(PNkx6.1 and Pax6 overlap)
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Neurites
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Growth Factors
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Nervous System Development
• Formation and differentiation of the neural tube
• Tissue architecture of the central nervous system
• Differentiation of neurons/generation of neural diversity
• Pattern generation in the nervous system
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Specificity of Axonal Connections
3 steps:1. PATHWAY SELECTION: route to a specific
region2. TARGET SELECTION: recognition of target
cells and formation of connections3. ADDRESS SELECTION: refinement of
synapses so that each axon contects to a small subset of its initial connections
• First 2 steps are independent of activity; final step often requires synchronized electrical potentials
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Pathway Selection
• Extracellular matrix proteins and growth factors provide navigation cues to growth cones
ECM(laminin vs. collagen)
Signalling molecules(ephrins, semaphorin, netrin and Split)
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Target selection
• Growth factors released from target tissues act over very short distances to either attract or repel axons during their final approach to the target
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Address Selection(activity dependent
refinement)• Competition between axons for
innervation less active synapses are eliminated
Neuronal cell death
• Target tissue regulates the number of axons innervating it via neurotrophic factor concentration
• Neurons that lose their target innervation die
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Visual System Development
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Central Auditory System Pathways