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Development Overview
Focus on the role of specific genes in organism segmentation.
Hox Genes: Multiple variants regulate segmentation.
Critical for proper bodily development.
Morphogens
Definition: Proteins secreted that freely diffuse throughout the developing embryo.
**Examples of Morphogen Types:
BMPs:** Localized in the posterior half of the embryo.
WMTS: Also localized in the posterior region.
E m x two morphogen:
Highly concentrated in the posterior, represented by red color coding in diagrams.
Function regulated by FGFs (Fibroblast Growth Factors) and EMPs (Ectodermal Morphogenetic Proteins).
Function of FGF: Suppresses translation of E m x two, resulting in lower expression in the anterior region.
Function of EMPs: Promotes E m x two expression on the posterior.
Expression Gradient: E m x two is expressed in a decreasing gradient from posterior to anterior.
Interaction of E m x two and Pax six
Role of E m x two:
Regulates the expression of Pax six morphogen.
E m x two suppresses Pax six on the posterior side where it is concentrated.
Pax six expression pattern:
High expression on the anterior side due to lower levels of E m x two.
Bidirectional Regulation:
Pax six inhibits E m x two production, creating a feedback loop.
Development of Brain Regions
Developmental significance of morphogens dictated by their concentration and regulation.
Embryo Development Stages:
Anterior develops into the forebrain.
Mid develops into the midbrain.
Posterior develops into the hindbrain and spinal cord.
Genetic Mutation Studies
Impact of E m x two Mutation: Results in alteration of brain development patterns.
Control Brain: Typical structure with defined frontal, motor, sensory, auditory, and visual cortices.
Mutant without E m x two:
Pax six is expressed everywhere leading to posterior brain regions reduced and anterior regions expanded.
Consequence of E m x two being essential for posterior brain development.
Impact of Pax six Mutation:
Results: Reduction in anterior brain regions and enlargement of posterior regions, showing its essential role in developing anterior brain areas.
Progenitor Cell Neuron Generation
Definition of Progenitor Cells: Cells that will develop into neurons, located in the neural tube.
Neuronal Generation Methodology:
Variability contributes to over 100 types of inhibitory neurons.
Focus on differentiation, localization, and migration of these cells during development.
Major Developmental Processes
Neurogenesis: The process of neuron birth.
Organized along the ventricular surface during early embryonic stages.
Cell Migration: Neurons migrate to their destinies post-birth.
Radial Migration: Excitatory neurons (specifically pyramidal neurons) migrate upwards along radial glia fibers to the cortex.
Developmental Timeline of Neuronal Birth
Neurogenesis Timeframe:
E 8-10: Progenitor cells attached to ventricular surface.
After division, newly born neurons migrate towards their final positions where they will reside at specific layers in the cortex.
Layer Formation: Inside-out manner, where:
Layer 6 (innermost) formed first, followed by subsequent layers (5, 4, 3, etc.).
Cell Division Types
Asymmetric Cell Division: Progenitor cells divide to form a new neuron that migrates while the progenitor remains.
Symmetric Cell Division: Both daughter neurons migrate post-division, affecting positioning in the brain.
Neuronal Development Techniques
Use of Green Fluorescent Proteins: Allows tracking of progenitor cell lineage in live developing tissues.
Tracks development and migration in real-time.
Migration Pathways
Radial Glial Migration: Primary pathway for pyramid neurons.
Utilized two motion modalities:
Soma Translocation: Cell body pulls itself toward the target region.
Glial Guided Migration: Neurons move along radial glial cells as guides.
Unique Sites of Neurogenesis
Remaining Progenitor Zones:
Limited to hippocampus (for memory) and olfactory bulbs (to maintain sense of smell) in mature brains.
Neurogenesis Role in Learning: Constant replenishment allows adaptation to new experiences.
Cajal-Retzius Cells Functionality
Localised Functions: Produce reelin, a protein that provides stop signals for migrating neurons, ensuring proper adherence to specified layers.
Effect of Reelin Deficiency: Results in severe disorganization of cortical layering and can lead to behavioral issues such as ataxia.
Genetic Modifications and Research Implications
Genetic modifications in animal models (e.g., mice) help illustrate the effects of specific genes on brain organization and functionality.
Disruption in reelin affects cortical organization without causing complete development failure or influencing neurogenesis negatively.