Download Development of Neural Circuits

Development of
Neural Circuits
Lesson 5
Stages of Cellular Activity
6 distinct stages
1. Neurogenesis
2. Cell migration
3. Differentiation
4. Synaptogenesis
5. Neuronal cell death
6. Synaptic rearrangement ~
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Neurogenesis
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Precursors (stem) cells
 Neural plate & tube stages
 Neural tube’s ventricular zone
 Induction signals ~
Symmetrical Mitosis
Results in 2 stem cells
 Slow & unlimited division
 Mediated by notch protein
 Required for self-renewal
 Stem & progenitor cells ~
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Asymmetrical Mitosis
Results in neuroblast + progenitor
 Neuroblasts
 Differentiate into neurons & glia
 Progenitors:
 rapid, but limited division
 Mediated by numb protein
 Asymmetrically distributed in mitosis
 Inhibits notch protein ~
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Neuronal Migration: PNS
Neural crest  PNS
 Initial position anterior-posterior factor
 Epithelial  mesenchymal transition
 Snail1 & 2   adhesion molecules
Guided by
cell adhesion molecules (CAMs)
Secreted peptide hormones
Along musculoskeletal tissues ~
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Neuronal Migration: CNS
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Neural tube  CNS
Primarily along radial glia
Some along axons
CAMs ~
Cell Migration
Long-distance
migration
 Along radial glia
 Tangentially to other
brain areas
 Cerebellar neuroblasts
 Mesoencephalon 
 Rhombencephalon ~
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Cell Differentiation
Stem cells  neurons & glia
 Many types of each
 Cell-to-cell signaling
 Particularly young precursor cells
 BMPs, shh, Wnt induction signals
 Cell autonomous
 Transcription regulation
 bHLH proneural genes  neurons
 Inhibit bHLH  glia ~
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Construction of Circuits
Linkage of neurons in different
regions
 Growth of axon from origin to
target
 Formation of appropriate synapses
 Cell-to-cell signaling
 Tropic factors
 Trophic factors ~
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Axon Guidance
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Axonal growth cone
Filopodia
Decision points
Decussate or not
Chemical cues
Ligands/receptors ~
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Non-diffusable cues
 CAMs
 Tropic & trophic
Diffusable chemical
signals
 Attraction
netrins

Repulsion
Semaphorins ~
Synaptogenesis
Superior cervical ganglion (PNS)
  eyes
  ear blood vessels
 After axons reach target
 Establish synapse
 Retract & regrow
 Do not form synapse ~
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Synaptogenesis
Neurotropic factors
 Ephrins & cadherins
 Specificity  ligand/receptor types
 Neurotrophic factors (neurotrophins)
 After synapse formation
 Cell-to-cell signals
 Nerve growth factor (NGF)
  neurite growth ~
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Apoptosis
Neuronal cell death
 programmed cell death
 20-80% of neurons in a region
 lack of neurotrophic factors
 Wrong or no connection
 neurons wither & die ~
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Synaptic Rearrangement
Competition
 elimination of synapses
 formation of new synapses
 Activity-dependent
 Neurotransmitter release
 Losing axon retracts
 May strengthen synapse at other
targets
 Winner  synapses at target ~
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