Nervous system development

Overview of Nervous System Development

  • The development of the nervous system occurs in 10 stages:

    1. Neural Induction

    2. Patterning

    3. Mitosis

    4. Migration

    5. Aggregation

    6. Differentiation

    7. Synaptogenesis

    8. Neuron Death

    9. Synapse Rearrangement

    10. Myelination

Neural Induction

Definition

  • Induction: The alteration of cell fate due to interactions with neighboring cells.

  • Components of Induction:

    • Inducer: Tissue that provides signals that change the cellular behavior of other tissues.

    • Responder: Tissue that responds to the signals from the inducer.

Morphogens

  • Morphogens are:

    • Soluble substances (proteins) that diffuse from their site of synthesis, creating a concentration gradient in developing tissue.

    • They direct cell differentiation, where cell fate is dependent upon the concentration of protein received.

Gastrulation

  • Gastrulation: Transition where the cells of the early embryo (blastula) rearrange into a multi-layered structure (three layers).

  • Importance: Lewis Wolpert noted, “It is not birth, marriage, or death, but gastrulation which is truly the important event in your life.”

  • Gastrulation accomplishes:

    1. Establishment of the three primary germ layers:
      a. Ectoderm - gives rise to skin, hair, and nervous system
      b. Mesoderm - gives rise to muscle and bones
      c. Endoderm - gives rise to the gastrointestinal system

    2. Establishes the basic body plan, including the physical construction of primary body axes.

    3. Cell movements during gastrulation place cells in new positions to interact with initially distant cells.

The Spemann-Mangold Experiments

  • Overview: An organizer graft induces a twinned axis.

  • The organizer region generates axial mesoderm during normal development.

    • Normal embryo - Donor embryo - Grafted organizer region promotes secondary axis formation in the host embryo.

Neurulation

  • Neurulation: The embryonic formation of the neural tube by the closure of the neural plate, directed by the underlying notochord.

    • Results in:
      a. Formation of the neural tube, which subsequently generates the mature central nervous system.
      b. Creation of the neural crest, which migrates away from the neural tube and gives rise to various cell types.
      c. Formation of the epidermis that covers the neural tube.

Timeframes

  • Neurulation occurs as follows:

    • Day 18: Neural tube formation begins.

    • Day 21: Key structures like the neural crest and notochord are evident.

Patterning

Definition

  • Patterning: The regional specification of the embryo to define the structure and organization of the nervous system, ensuring spatial organization where cells possess a “molecular address.”

Importance of Patterning

  1. Enables precise organs and systems to develop by organizing cell types to specific locations.

  2. Plays a crucial role in ensuring proper neuron types connect to specific brain regions in a topographic manner.

  3. Influenced by molecular signals like retinoic acid, noggin, and Sonic hedgehog, which involved in various signaling mechanisms and gradients.

Anatomo-Functional Axes in Animals

  1. Dorsal-Ventral (D-V)

  2. Rostral-Caudal (R-C)

  3. Medial-Lateral (M-L)

Anatomical Planes

  • There are three planes in anatomy:

    1. Horizontal Plane

    2. Coronal Plane

    3. Sagittal Plane

    • Mid-sagittal and Peri-sagittal variants exist.

Mitosis and Proliferation

Mitosis

  • Occurs in the ventricular zone at a rate of 250,000/min.

    • Post-mitosis, daughter cells become fixed or post-mitotic.

Types of Progeny

  • Progeny from mitosis can be distinct:

    • Symmetrical: Producing two mitotically active daughter cells.

    • Asymmetrical: Yielding one active cell and either a neuron or glial cell.

Cell Types

  • There are various stem cell types:

    • Neuroblasts

    • Glioblasts

    • Astrocytes

    • Oligodendrocytes

Migration

Migration Patterns

  • Neuronal migration occurs in two primary patterns:

    1. Radial Migration: Cells move along radial glial cells (locomotion).

    2. Tangential Migration: Cells migrate horizontally across the developing brain.

Mechanisms of Migration

  • Radial migration has two key processes:

    1. Nuclear translocation (somal translocation)

    2. Cell migration using radial glial cells

Aggregation

Process of Aggregation

  • Aggregation: Similar neurons move together to form layers or small groups termed nuclei.

  • Inside-out rule: Neurons migrate to specific locations based on the developmental stage.

Differentiation

Overview

  • Post-mitotic cells begin specializations into three basic cell types:

    1. Neurons

    2. Astrocytes

    3. Oligodendrocytes

  • Mature neurons feature distinct morphologies:

    • Axons

    • Dendrites

    • Soma (Cell bodies)

Growth Cones and Guidance

  • Growth Cones: Structures at the tips of axons enabling navigation towards targets.

    • Mechanisms involved:

    1. Pioneer axons lead the way.

    2. Segmented paths formed by pioneers.

    3. Signals are a mix of short-range and long-range interactions (positive and negative).

Synaptogenesis

Synapse Formation

  • Synaptogenesis: The process through which neurons establish synaptic connections.

    • Maturation of synapses includes the development of pre and post-synaptic specializations for efficient signal transmission.

Neuron Death

Neuron Survival Rates

  • During embryonic and fetal development, between 40% and 75% of neurons do not survive due to inadequate synaptic connections.

Neurotrophic Hypothesis

  • Proposes that neuron populations are matched to their target cells, where cell death ensures integration and efficiency in neural networks.

Synapse Rearrangement

Refinement Process

  • Active synapses may uptake neurotrophic factors, ensuring their stability, whereas inactive synapses could fail due to insufficient trophic support.

Myelination

Myelination Definition

  • Myelination is the process where Schwann Cells and Oligodendrocytes envelop axons with a myelin sheath, enhancing signal conduction speed.

Development Timeline

  • Myelination progresses alongside neurogenesis and synaptogenesis:

    • Details include the age at which myelination occurs and its correlation with increased white and gray matter volumes.