20 - Neurogenesis - Part 2

  • Neuronal Birth and Migration

    • Neurons are produced in the peripheral zone and migrate radially to their designated areas.

    • Migration is directed by radial glia, which serve as progenitor cells.

    • Progenitors are multipotent, meaning they can generate various neuron types and glia.

  • Cell Fate Determination

    • Emphasizes the temporal determination of cell fate in neurons and glial cells.

    • Glial cells are the last to be produced, with remaining radial glia differentiating into astrocytes.

  • Cortical Development

    • Features of cortical development include the inside-out formation of layers where neurons migrate past earlier cortical plates.

    • Neuron numbers are enhanced by proliferation in the subventricular zone.

    • Important neuronal derivatives from the ganglionic eminence include inhibitory neurons and oligodendrocytes.

    • The sequence of maturation in neurons follows a temporal pattern: first efferents (sending signals), then afferents (receiving signals), and associational neurons, followed lastly by glia.

Additional Recap on Cortical Development

  • Key points reiterate the temporal specification of cell fate and radial migration from the ventricular zone, producing projection neurons.

  • Inhibitory interneurons are derived from the ganglionic eminence during cortical development, with glia being the last to differentiate.

  • Oligodendroglia also arise from the ganglionic eminence.

Overview of Neurogenesis

  1. Invertebrate Model Systems

    • Neurogenesis in Caenorhabditis elegans (roundworm) and Drosophila melanogaster (fruit fly).

    • Notch signaling is pivotal for neurogenesis.

  2. Neurogenesis in Mammals

    • Occurs within the ventricular zone of the neural tube.

    • Pertains to the development of the cerebral cortex, including radial glia and cortical layer formation.

    • The significance of the ganglionic eminence in neurogenesis.

  3. Neurogenesis in the Neural Crest

    • Discusses adult neurogenesis.

Ganglionic Eminence (GE)

  • The ganglionic eminence is a transient structure crucial for neuronal development, aiding in the migration of cells and axons.

  • Internuero Migration

    • Interneurons migrate tangentially from the ganglionic eminence to the cerebral cortex, moving perpendicular to radial glia.

    • In contrast, radially migrating interneurons travel parallel to radial glial cells.

Categorization of Ganglionic Eminence

  • Medial Ganglionic Eminence (MGE)

    • GABAergic interneurons migrate tangentially to reach the cortical anlage.

  • Cortical Ventricular Zone

    • Glutamatergic neurons destined for the cortex originate locally and migrate radially.

  • Considered a coronal section in an embryonic mouse, illustrating the various ganglionic eminences:

    • Medial Ganglionic Eminence (MGE)

    • Lateral Ganglionic Eminence (LGE)

    • Caudal Ganglionic Eminence (CGE)

Neurogenesis in the Neural Crest

  • Overview

    • Somites, which are mesoderm blocks beside the neural tube, are crucial for developing various vertebrate structures.

    • They guide neural crest cell migration.

EMT and Migration in Neural Crest

  • Epithelial-Mesenchymal Transition (EMT)

    • EMT describes molecular events transforming epithelial cells into a migratory mesenchymal phenotype.

    • This phenotype is defined by reduced cell adhesion and a transition to a spindle-like shape.

  • MMPs (Metalloproteinases)

    • MMPs are responsible for degrading proteins in the extracellular matrix, an essential step in EMT.

    • For example, MMP9 can degrade cell adhesion molecules like N-cadherin, facilitating cell separation during migration.

Neural Crest Migration Paths and Derivatives

  1. Neural crest subpopulations

    • Cells along the anterior-posterior axis have distinct migration pathways and fates:

    • Cranial, Trunk, Vagal, and Sacral Neural Crest

    • Contributions to diverse structures:

      • Craniofacial structures, neurons, melanocytes, Schwann cells, and various ganglia.

  2. Extracellular Matrix Interactions

    • Certain ECM molecules, such as fibronectin and laminin, promote neural crest cell migration, while others like ephrins inhibit it.

    • Ephrins can block migration across posterior somite regions:

      • Example: Eph2B and Sem3F are identified inhibitors.

Specific Neural Crest Derivatives

  • Cranial Neural Crest Fates Include:

    • Parasympathetic ganglia

    • Schwann cells (including placode-derived ganglia)

    • Melanocytes

    • Connective tissues of cranial structures, glands, skin, and muscles.

  • Trunk Neural Crest Contributions:

    • Sensory ganglia (DRG), sympathetic ganglia, adrenal medulla, and enteric nervous system components.

Factors Influencing Neural Crest Cell Fates

  1. Local Signals

    • Fate determination based on local environmental signals in different body regions.

    • Transplant experiments demonstrate variability in neural crest fate based on location:

      • Ectopic cartilage formation upon transplantation between regions.

  2. Key Signaling and Transcription Factors

    • Various signaling pathways (e.g., BMP, Wnt, Notch, FGF) and transcription factors (e.g., Pax3/7, SoxE, etc.) dictate neural crest cell behavior and differentiation.

Adult Neurogenesis Overview

  • Adult neurogenesis predominantly occurs in:

    • Subventricular Zone & Hippocampus

  • The study of adult neurogenesis has revealed significant neural plasticity.

    • Sensory neuron generation and its integration into existing neural circuits are key areas of research.

Quiz Questions

  1. Question-1: Which type of migration do glutamatergic neurons show?

    • Choices:
      A. Radial migration
      B. Tangential migration
      C. Both A and B
      D. None of the above

  2. Question-3: Which parts of the brain are predominantly studied for adult neurogenesis?

    • Choices:
      A. Hippocampus
      B. Cerebellum
      C. Subventricular zone
      D. Both A and C