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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.