Neuro Development

Context of Experimentation: Understanding misorganization of cell types through experimental analysis.
- Key Question: How do we verify the disorganization of neurons in developmental biology?
- Method: Use of antibodies to analyze protein distribution in tissue.

Example Image Analysis: Fluorescent imaging of tissue from adult animals.
- Top Panel: Tissue from a wild type (normal developing animal).
- Demonstrates well-organized layers of neurons (cortex, layers one through six).
- Each color represents a different subtype of neurons (e.g., blue, green, red, magenta).
- Bottom Panel: Tissue from a mutant (disorganized neuron structure).
- Exhibits lack of organization in neuronal axons.
- No defined barrel fields, showing randomness in the arrangement of neurons and their axons.

Barrel Fields: Specific organization in somatosensory cortex related to sensory perception from facial whiskers.
- Each barrel corresponds to a single whisker and its sensory input to the cortex.
- Wild type shows clear cylindrical areas (barrels) where specific sensory input is processed.
- Mutants show chaotic axonal connections leading to disorganized sensory processing.

Excitatory Neurons: Origin and migration specifics.
- Born near the ventricular zone; perform radial migration after division.
Inhibitory Neurons: Developmental origin and migration strategies.
- Key cell types include: chandelier cells and basket cells (e.g., expressing CCK).
- Migration often involves positions established as the brain develops.

Radial Migration: Defined path taken by excitatory neurons originating from the ventricular surface.
- Visual representation indicating the trajectory of these neurons.
Tangential Migration: Describes path of inhibitory neurons mainly sourced from medial ganglionic eminence (MGE) and others.
- Neurons migrate ventrally, making turns to reach their final destinations (cortex).

Inhibitory Neuron Origins:
- 70% sourced from MGE, remaining from caudal ganglionic eminence (CGE).
- Subsequent turn migrations characterized.

Excitatory vs. Inhibitory Migration:
- Excitatory neurons ascend vertically whereas inhibitory neurons make turns during migration.
- Experimental tracing (e.g., GFP labeling) provides visual tracking of migration.

Key Morphogen: Sonic Hedgehog (Shh)
- Affects developmental processes and neuron subtype determination.
Morphogen Pathways:
- Example: Anti-X2.1 promotes development in specific neuronal regions (MGE).
Implications of morphogen functions: Regulation of gene expression and neuronal subtype development.

Developmental Phases:
- Early: Asymmetric cell division leads neurons to layer six of the cortex.
- Later: Symmetrical division and movement of neurons to upper layers of the cortex.
Inside-Out Development:
- Neurons in the cortex develop from deepest layers (layer six) outward to nearer layers.

Birth Dating: Used to track neuron development in a controlled experiment.
- Procedure: Injection of radioactive tracers into pregnant rodents at specific embryonic days (e.g., day 11, 13, 15).
- Neonates are born and allowed to develop for tracking.
Results Documentations:
- Radioactive labeling revealed localization patterns (layer six for early injections).
- Subsequent injections yielded traces in higher layers, confirming inside-out development.

Neural Organization: Highly regulated, stepwise, and layered development of the nervous system.
Importance of Genes and Morphogens: Critical for proper neuron generation and migration paths.
Morphogens mediate various signaling pathways essential for neuronal growth and organization.

Understanding of circuit complexity hinges on recognizing variation in neuronal types and their migrational pathways, contributing to the comprehensive mapping of neural development.