Development+I_2Slides

Development of the Brain

  • Five Fundamental Processes:

    1. Neural Induction: Specifies a region of embryonic ectoderm to form the neural ectoderm.

    2. Proliferation and Migration: Generation of all neurons and glial cells in the nervous system.

    3. Neuronal Pathfinding: Extension of axons to their targets to form synapses.

    4. Synapse Formation and Elimination: Synaptogenesis followed by the elimination of unused synapses.

    5. Cell Death: Up to 50% of neurons die in many regions of the brain.

Induction of Nervous System

  • Induction: Interaction between embryonic regions that influences differentiation.

  • Classic Experiments: Indicate that nervous system induction occurs during gastrulation.

  • Gastrulation: Rearrangement of cells into germ layers (mesoderm, endoderm, ectoderm).

Development of the Human Brain

  • Begins forming at approximately 2-3 weeks old:

    • Dorsal surface thickens to form a neural tube surrounding a fluid-filled cavity.

    • The anterior enlarges to differentiate into the hindbrain, midbrain, and forebrain.

    • The remaining neural tube becomes the spinal cord.

Early Development of the Central Nervous System

  • Human Embryonic Disc (14 days, ~0.4 mm):

    • Primitive Streak: Initiates gastrulation.

  • Gastrulation (Days 14-15): Cells migrate underneath the epiblast to form trilaminar embryo.

Mesoderm and Notochord Formation

  • Mesoderm Differentiation: Begins on Day 17-18.

  • Notochord Formation: Releases proteins (e.g., noggin, Cerberus) that influence ectoderm and induce nervous tissue.

Neurulation: Formation of the Nervous System

  • Notochord Signals: Releases proteins to overlying ectoderm.

  • Ectoderm folds to form a neural tube, pinching off to create the peripheral nervous system.

Notable Experiments in Induction

  • Spemann and Mangold's Work: Discover the 'embryonic organizer' by transplanting notochord tissue.

    • Resulted in a second nervous system developing in the host embryo.

Neuronal Growth and Axon Pathfinding

  • Axons extend towards their targets following protein gradients.

  • Growth Cone: The motile tip of axons remodels its cytoskeleton in response to guidance cues.

  • Guidance Cues:

    • Netrins: Attract axons.

    • Slits, Ephrins, Semaphorins: Generally repel growth cones.

Neuronal Connectivity and Synaptic Plasticity

  • Axons initially form synapses with multiple targets.

  • Postsynaptic Cells: Strengthen connections with certain axons while eliminating others based on input patterns.

  • Neuronal Death: Natural part of development; neurons that fail to establish proper connections undergo apoptosis.

Neuronal Growth Factors

  • Nerve Growth Factor (NGF): Discovered by Rita Levi-Montalcini, promoting survival and growth of neurons.

  • NS Growth factors play a crucial role in the matching of neuron count to the number of target cells.

Neurotrophins

  • Family of proteins (e.g., NGF, BDNF) essential for neuron survival after connections are made.

    • Failure to connect leads to apoptosis.

Theoretical Concepts: Neural Darwinism

  • Proposed by Gerry Edelman, it describes a selection process among synaptic connections whereby stronger connections are preserved while weaker connections are eliminated.