Neuro development

Development of Organisms

• Embryonic development is guided by specific genes.

  • Hox Genes:

  • Multiple variants determine proper segmentation of organism.

  • Responsible for development of different body parts.

Morphogens

• Definition: Proteins that are secreted and freely diffuse throughout the developing embryo.

• Example: Involved in defining different morphologies.

• Localization of different morphogens:

  • BMPs and WNTs:

  • More concentrated in the posterior of the embryo.

  • EGF (embryonic morphogen x2):

  • Regulated in concentration by various morphogens.

  • Expressed in a gradient from posterior (high concentration) to anterior (no expression).

Regulation of Morphogen Concentrations

• FGFs:

  • Suppress translation of EGF.

  • Leads to lower EGF expression in the anterior part of the embryo.

• EMPs and WNTs:

  • Promote the expression of EGF in the posterior region.

Function of EGF

• EGF regulates another morphogen called Pax6:

  • High concentration of EGF on the posterior suppresses Pax6 expression.

  • Low concentration (anterior side) promotes high expression of Pax6 since EGF cannot inhibit it there.

• Pax6:

  • Plays a role in brain region formation.

  • Also inhibits further expression of EGF, creating a feedback loop in development.

Developmental Pathways

• Interaction between EGF and Pax6 demonstrates a regulatory pathway essential for proper organism formation.

• Mutations in genes related to morphogens disrupt development:

  • Example:

  • Mutating EGF leads to lack of regulation of Pax6, resulting in:

    • Overexpression of Pax6 everywhere (anterior and posterior).

    • Posterior regions of brain diminish while anterior areas enlarge.

  • Conclusion: EGF is crucial for proper development of posterior brain structures.

Neuronal Development in the Brain

• Generation of different types of neurons occurs from progenitor cells localized in the neural tube.

• Progenitor Cells:

  • Responsible for producing neurons and are found in specific regions of the embryo.

  • Experience organized processes of neurogenesis (neuron birth) followed by migration to their final positions.

Neuronal Birth and Migration

• Neurogenesis:

  • Refers specifically to the birth of neurons.

• Neurons are generated in an organized manner from progenitor cells located at the ventricular surface.

  • Initially, progenitor cells attach to the ventricle surface and the outer layer of the embryo.

  • During the early stages of development, progenitor cells divide and give birth to future neurons.

  • Neurons migrate along fiber-like structures created by radial glia.

Migration Mechanisms

• Radial Glia:

  • Serve as scaffolding for migrating neurons, assisting in their proper localization in the cortex.

• Inside-out Development:

  • Neurons are born numerically from inner layers outward to form layers of the cortex:

  • First layer: Layer 6 (innermost)

  • Subsequent layers: Differentiated above the previous.

Methods of Studying Neuronal Development

• Labeling with GFP (Green Fluorescent Protein):

  • Allows tracking of progenitor cells and their neuronal derivatives over time.

  • Studying these labeled cells enables researchers to understand migration patterns.

Types of Neuronal Migration

• Radial Migration:

  • Mainly for excitatory (pyramidal) neurons, traveling upward toward the cortex.

  • Involves two types of movement:

  1. Soma translocation:

     • The soma follows processes out to the marginal zone, pulling itself up after reaching the target destination.

  2. Glia-guided migration:

     • Newly formed neurons move along radial glial cells directly to their destination.

• Symmetric vs. Asymmetric Cell Division:

  • Asymmetric Division: One cell remains a progenitor; the other becomes a neuron.

  • Symmetric Division: Both cells migrate together after division.

Role of Different Neurons and Their Migration

• Excitatory neurons use radial migration to reach their positions, while inhibitory neurons follow different routes (tangential migration).

• Recent studies explore the behavior and function of pairs of neurons originating and migrating together, suggesting possible functional connections.

Factors Influencing Neuronal Development

• Rulin and Cajal-Retzius Cells:

  • Cajal-Retzius cells produce rulin, a signaling protein guiding migration and final positioning of neurons.

• Mutations in Developmental Genes:

  • Genetic modifications in rulin profiling lead to disorganized neuron distribution within cortical layers:

  • Shows importance in cellular organization but not in neurogenesis.

Neurogenesis in Specific Brain Regions

• Continuous neurogenesis occurs mainly in:

  • Hippocampus:

  • Important for memory formation, where new neurons help assimilate new experiences.

  • Olfactory Bulb:

  • To replace damaged olfactory receptors often exposed to environmental stressors.

• Discusses relevance of maintaining neurogenesis for lifelong learning and adaptation.