Development

Understanding Neural Development

  • Importance of Studying Neural Development

    • Understanding causes and implications of birth defects.

    • Birth defects caused by abnormal developmental processes.

    • Example of spina bifida.

    • Zika virus implicated in causing microcephaly through infection of radial glia, leading to decreased cortical expansion.

    • Potential of stem cells in treating neurological conditions.

    • Applications in treating conditions like Parkinson’s disease and spinal cord injury.

    • Investigation of neurogenesis in adults.

    • Concept of plasticity recapitulating ontogeny.

    • Similarity of mechanisms for plasticity in adult brain to those in development.

    • Analysis of potential for regeneration after injuries or diseases.

Overview of Nervous System Development

  • Formation of Neural Tube

    • Overview of how the brain and spinal cord (CNS) are derived from the neural tube.

    • Peripheral nervous system originates from the neural crest.

  • Neurogenesis and Gliogenesis

    • Cell division and differentiation leading to increased neuronal numbers and expansion of brain vesicles.

    • Importance of cell migration for appropriate neural connections.

    • Processes involved include axon pathfinding and synaptogenesis.

Formation of the Neural Tube

  • Source of Nervous System Cells

    • Brain and spinal cord are formed from the neural tube.

    • The peripheral nervous system derives from the neural crest.

    • Breakdown of brain structures:

    • Telencephalon: Forms cerebral hemispheres.

    • Diencephalon: Yields thalamus and hypothalamus.

    • Hindbrain: Comprises brain stem and cerebellum.

  • Consequences of Neural Tube Closure Failures

    • Spina Bifida

    • Most common defect from caudal closure failure.

    • Anencephaly

    • Failure of rostral end to close.

    • Statistics of Neural Tube Defects

    • Occurrence is approximately 1 in 1000 births.

    • Adequate folic acid intake can prevent approximately half of neural tube defects (closure by 28 days in humans).

Neurogenesis Explained

  • Initial Steps in Neural Development

    • Formation of the neural tube and subsequent cell proliferation.

    • Increased surface area achieved through division of radial glial cells.

    • Comparison of expansion in forebrain vs. spinal cord regions.

  • Mechanisms of Neuron Development

    • Structure expansion is attributed to both symmetrical and asymmetrical division of radial glial cells.

    • Cell Proliferation

    • Symmetrical division results in two daughter cells remaining radial glial cells.

    • Asymmetrical division produces one radial glial cell and one neural precursor.

Zika Virus and Microcephaly

  • Relation Between Zika Virus Infection and Microcephaly

    • Zika virus infects radial glial cells and interferes with cell division, reducing cortical area expansion.

Mechanisms of Neuron Differentiation and Fate

  • Inductive Signals in Neurogenesis

    • Stem cells can expand the cerebral cortex through symmetrical division leading to an increase in precursor cells.

    • Asymmetric divisions lead to neuroblast formation, with neuroblasts migrating to specific cortical layers.

    • The differentiation into neurons is highly influenced by location and local environmental signals.

  • Gene Influence on Neurogenesis

    • The gene Aspm is under selection in primate evolution influencing symmetrical cell division, affecting cortex thickness and surface area.

Experimental Techniques in Neurogenesis

  • Determining Neuron Birthdates

    • Use of BrDU (Bromodeoxyuridine) to label dividing cells and ascertain neuron birthdates.

    • Strong labeling indicates neurons that have ceased to divide, while continued division results in lesser labeling.

  • Building of the Cerebral Cortex

    • Understanding the inside-out pattern of cortical neuron migration where later-born neurons migrate past earlier-born ones.

    • Effects of injections of radioactive thymidine to trace development timelines.

Migration and Development Patterns

  • Radial Migration of Neurons

    • Pyramidal cells and astrocytes migrate vertically along radial glial fibers from the ventricular zone.

    • Inhibitory interneurons and oligodendroglia have different migratory paths, originating from distinct regions.

  • Lis1 Gene Mutations

    • Study of mutations impacting the migration of neuronal precursors, which provides insights into the arrangement of neuronal layers in mutants compared to normal development.

Axonal Navigation Mechanisms

  • Growth Cones in Axonal Navigation

    • Growth cones act as sensory and motor structures at the tips of axons, responding to environmental cues.

    • Cues include:

    • Chemotaxis: directed movement in response to chemical gradients.

    • Repulsion and Adhesion: growth cones can either be attracted or repulsed by local cues.

  • Regulatory Mechanisms

    • The motility of growth cones is managed by extracellular signals, impacting actin dynamics and microtubule behavior, directly influencing axon growth and guidance.

  • Example of Axonal Navigation in Pain Neurons

    • Investigation of how second-order pain neurons navigate toward the brain involving receptor expression for signaling pathways.

  • Retinogeniculocortical Pathway in Mammals

    • Understanding the decision-making process of retinal axons regarding crossing pathways, distinguishing nasal vs. temporal retinal ganglion cells.