upcoming sessions april 22:nervous system development lecture april 24:reviews of axonal pathfinding...
TRANSCRIPT
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
Inner ear developmentNervous system development
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
Chick Embryo Whole Mounts
Primary Neurulation(formation of neural tube)
MHP=medial hinge point
Neural groove
Primary Neurulation (cont’d)
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
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
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
Human Brain Development
Neural Stem Cells andthe Location of Dividing Cells
Cell Migration
After their terminal division, cells migrate from the lumen toward the surface
Lamination
Cells with the earliest birthdays migrate the shortest distances
Adult Stem Cells
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
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
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
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
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
Paracrine Factor Gradients
Motor neurons(PNkx6.1 and Pax6 overlap)
Neurites
Growth Factors
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
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
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)
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
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
Visual System Development
Central Auditory System Pathways