Development
Cortical Radial Unit Hypothesis
The cortical radial unit hypothesis suggests that a radial column of the cortex comes from the same location in the ventricular zone.
Neurite & Symmetrical Cleavage:
Daughter cells exhibit different transcription factors (TFs).
The human cortex is significantly larger due to evolutionary factors.
Key Components:
Site radial Notch: Symmetrical division influenced by transcription factors including EMX2 and Pax6.
EMX2 is primarily involved in posterior development, while Pax6 is involved in anterior cortex development along the anterior-posterior (A-P) axis.
Neuronal Fate Decisions:
Neurons destined for the anterior cortex show higher levels of Pax6.
Notch signaling promotes the maintenance of progenitor cells in the posterior cortex.
Posterior cortex neurons exhibit higher levels of EMX2 and differentiate into astrocytes if EMX2 expression is low.
This leads to smaller posterior cortical areas and larger anterior regions.
Numb Protein:
Acts as a neural gate for fate determination during cleavage.
Pax6 Knockout Consequences:
Causal effect: Causal growth of posterior areas and shrinkage of anterior cortex.
Location in the ventricular zone influences thalamic organization and recruitment of thalamic neurons to corresponding subplate areas.
Neural Pathways Development
Pathway Selection:
Pathway selection involves making decisions along the proliferative zone, which is influenced by location, cell type, and cell-cell signaling.
Example: Origin of pyramidal neurotransmitters and astrocytes along the optic stalk shows three path choices:
Enter optic tract on the same side.
Enter the opposite side.
Navigate through different optic nerves.
These decisions are influenced by extrinsic signals and local extracellular conditions along the subventricular zone.
Target Selection:
Determines the specific area of the brain to innervate.
Example: Selecting the correct thalamic nucleus, where neural precursor cells migrate along radial glial fibers to reach the lateral geniculate nucleus (LGN).
Address Selection:
Final decision on which part of the cortex or brain to innervate.
Example: Sorting and retraction of retinal axons aids in establishing retinotopy.
Neurite Growth Mechanisms
Growth Cones:
Neurite ends that identify targets using growth cues which help navigate towards synaptic targets.
Cellular Structures:
Lamellipodia: Flat sheets that undulate to explore the environment.
Filopodia: Projections that sample the local environment and grab substrate to elongate the axon.
Guidance Cues:
Permissive and Inhibitory Signals:
Neurites encounter a combination of permissive (growth-accommodating) and inhibitory signals that form guidance corridors.
CAMs (cell-adhesion molecules) help axons stick to the correct pathway.
Extracellular Signals:
Semaphorin 30:
A repulsive signal secreted by cells in the marginal zone that directs pyramidal axons downward while attracting dendrites.
Neural Development and Regeneration
Pioneer Axons:
Establish pathways for follower axons.
Example: In frogs, pioneer axons in the tectum receive inputs from the contralateral eye, using environmental cues for navigation.
Chemoattraction and Repulsion:
Netrins: Chemotactic signals that attract certain axons, facilitating growth into the anterior tectum.
Slit: A repulsive signal that guides axons by creating gradients leading to correct decussation.
Synapse Formation:
Neuromuscular junctions involve presynaptic and postsynaptic proteins that communicate neurotransmission.
Ephrin B:
Important in determining decussation patterns; secreted in gradients to modulate axonal pathways.
Neurogenesis and Neural Repair Mechanisms
Neurogenesis Discovery:
Joseph Altman in the 1980s initially described adult neurogenesis. Dr. Elisabeth discovered it in specific brain regions, namely the hippocampus and olfactory bulb.
Method to Identify Neurogenesis:
BrdU assay: A method to identify new neurons by incorporating bromodeoxyuridine (BrdU) during DNA synthesis in dividing cells.
Neurogenesis Process:
Precursor cells along the lateral ventricle migrate into designated areas (e.g., olfactory bulb) via the rostral migratory stream.
Some neurons in specific regions like the dentate gyrus of the hippocampus adopt GABA-ergic identities.
Cortical Radial Unit Hypothesis
The cortical radial unit hypothesis suggests that a radial column of the cortex comes from the same location in the ventricular zone.
Neurite & Symmetrical Cleavage:
Asymmetrical cleavage: Produces daughter cells with different fates and varying transcription factor profiles.
Daughter cells exhibit different transcription factors (TFs).
The human cortex is significantly larger due to evolutionary factors.
Key Components:
Site radial Notch: Symmetrical division influenced by transcription factors including EMX2 and Pax6.
EMX2 is primarily involved in posterior development, while Pax6 is involved in anterior cortex development along the anterior-posterior (A-P) axis.
Neuronal Fate Decisions:
Neurons destined for the anterior cortex show higher levels of Pax6.
Notch signaling promotes the maintenance of progenitor cells in the posterior cortex.
Posterior cortex neurons exhibit higher levels of EMX2 and differentiate into astrocytes if EMX2 expression is low.
This leads to smaller posterior cortical areas and larger anterior regions.
Numb Protein:
Acts as a neural gate for fate determination during cleavage.
Pax6 Knockout Consequences:
Causal effect: Causal growth of posterior areas and shrinkage of anterior cortex.
Location in the ventricular zone influences thalamic organization and recruitment of thalamic neurons to corresponding subplate areas.
Neural Pathways Development
Pathway Selection:
Pathway selection involves making decisions along the proliferative zone, which is influenced by location, cell type, and cell-cell signaling.
Example: Origin of pyramidal neurotransmitters and astrocytes along the optic stalk shows three path choices:
Enter optic tract on the same side.
Enter the opposite side.
Navigate through different optic nerves.
These decisions are influenced by extrinsic signals and local extracellular conditions along the subventricular zone.
Target Selection:
Determines the specific area of the brain to innervate.
Example: Selecting the correct thalamic nucleus, where neural precursor cells migrate along radial glial fibers to reach the lateral geniculate nucleus (LGN).
Address Selection:
Final decision on which part of the cortex or brain to innervate.
Example: Sorting and retraction of retinal axons aids in establishing retinotopy.
Neurite Growth Mechanisms
Growth Cones:
Neurite ends that identify targets using growth cues which help navigate towards synaptic targets.
Cellular Structures:
Lamellipodia: Flat sheets that undulate to explore the environment.
Filopodia: Projections that sample the local environment and grab substrate to elongate the axon.
Guidance Cues:
Permissive and Inhibitory Signals:
Neurites encounter a combination of permissive (growth-accommodating) and inhibitory signals that form guidance corridors.
CAMs (cell-adhesion molecules) help axons stick to the correct pathway.
Extracellular Signals:
Semaphorin 30:
A repulsive signal secreted by cells in the marginal zone that directs pyramidal axons downward while attracting dendrites.
Neural Development and Regeneration
Pioneer Axons:
Establish pathways for follower axons.
Example: In frogs, pioneer axons in the tectum receive inputs from the contralateral eye, using environmental cues for navigation.
Chemoattraction and Repulsion:
Netrins: Chemotactic signals that attract certain axons, facilitating growth into the anterior tectum.
Slit: A repulsive signal that guides axons by creating gradients leading to correct decussation.
Synapse Formation:
Neuromuscular junctions involve presynaptic and postsynaptic proteins that communicate neurotransmission.
Ephrin B:
Important in determining decussation patterns; secreted in gradients to modulate axonal pathways.
Neurogenesis and Neural Repair Mechanisms
Neurogenesis Discovery:
Joseph Altman in the 1980s initially described adult neurogenesis. Dr. Elisabeth discovered it in specific brain regions, namely the hippocampus and olfactory bulb.
Method to Identify Neurogenesis:
BrdU assay: A method to identify new neurons by incorporating bromodeoxyuridine (BrdU) during DNA synthesis in dividing cells.
Neurogenesis Process:
Neural precursor cells along the lateral ventricle migrate into designated areas (e.g., olfactory bulb) via the rostral migratory stream.
Some neurons in specific regions like the dentate gyrus of the hippocampus adopt GABA-ergic identities.
Neurons complete differentiation: After migration and adopting identities, neurons mature and integrate into functional circuits.