CNS Development Overview

Development of the Central Nervous System

• The central nervous system (CNS) continues to develop throughout life, not just during prenatal and childhood stages.
• Prenatal development, childhood development, and adulthood are key topics of CNS development.
• Disorders of neurodevelopment, such as Autism Spectrum Disorder and Williams Syndrome, are also addressed.

Historical View of CNS Development

• Historically, the CNS was viewed as a stable, fixed organ by adulthood.
• However, modern understanding encompasses brain plasticity, demonstrating continuous changes throughout life.

Current, Comprehensive View of CNS Development

• The development of the CNS involves an ongoing interaction between genes and the environment, from prenatal (in utero) stages, through childhood, to adulthood.

Genes and Environment: The Case of "Genie"

• The case of "Genie" highlights the critical role of environmental experience in CNS development, although stories about such cases often don't show the full picture.

Prenatal Development of the CNS

• Gametogenesis (through meiosis) involves the creation of egg and sperm, leading to fertilization, which produces a zygote.
• Mitosis occurs after fertilization, producing multiple cells.

After Formation

• Once cells develop, they must differentiate into their specific cell types (e.g., muscle, liver, neurons, glia).
• They need to migrate to their appropriate locations.
• Cells must establish functional connections with other cells.

Embryonic Development of the Nervous System

• Key stages in embryonic nervous system development: neural plate induction, neural proliferation, migration and aggregation, axon growth and synapse formation, and neuron death and synapse rearrangement.

Induction of the Neural Plate

• Induction of the neural plate originates from ectoderm cells, leading to the creation of the neural groove. Then the neural groove folds in to create a neural tube.
• This occurs through chemical signals originating from adjacent mesoderm cells.
• The neural tube develops specific components: a central canal and neural crest.

Neural Proliferation

• During neural tube development (around 40 days post-fertilization), ectodermal tissue differentiates into three vesicles.
• Neural proliferation peaks shortly after neural tube closure.
• Chemical signals influence and regulate the process of neural tube development.
• Development proceeds in an anterior-to-posterior manner.

Migration and Aggregation

• Migration involves the movement of newly formed cells to their correct positions, often guided by chemical signals.
• Types of migrations include: Radial, Tangential, and Multipolar migration.
• Aggregation involves cell clustering and connections.

Cell Adhesion Molecules

• Cell adhesion molecules (CAMs) are crucial components in the interactions of aggregating cells and promoting recognition
• Gap junctions facilitate communication and connections between cells.

Disorders of Neuron Migration

• Kallmann syndrome is characterized by abnormal genitals and a dysfunctional sense of smell.
• Lissencephaly results from cytoskeleton defects obstructing neuronal migration.
• Other disorders (Schizophrenia, Bipolar Disorder, Autism Spectrum Disorders, Dyslexia) may also be linked to neuron migration issues.

Axon Growth and Synapse Formation

• Axon growth originates from the axon growth cone extending and retracting filopodia.

How Growth Cones Find Their Target

• Chemoaffinity Hypothesis: suggests target-specific chemical labels guide axon growth.
• Topographic Gradient Hypothesis: proposes intersecting gradients (up-down and left-right) of chemicals guide axons.

Evidence for the Chemoaffinity Hypothesis

• Sperry's study of eye rotation and regeneration in frogs demonstrates the importance of specific chemical labels in axon guidance.

Evidence Contradicting the Chemoaffinity Hypothesis

• In cases where transplanted targets receive incorrect innervation, the chemoaffinity hypothesis is challenged.
• The route to the target is often circuitous, not linear.

Revised Chemoaffinity Hypothesis

• Pioneer growth cones initially follow chemical gradients.
• Subsequent growth cones follow pioneer growth cones via fasciculation (axons following previous axons).

Topographic Gradient Hypothesis

• Intersecting chemical gradients guide axonal growth between different regions.
• The maintenance of topographic integrity is vital for correct functionality of neural structures like the optic tectum, and is supported by the presence and differentiation of ephrin molecules.

Synapse Formation

• Requires neuron-neuron communication.
• Glia cells (astrocytes) support the development of synapses.
• In vitro and in vivo studies highlight the role of astrocytes in promoting and inhibiting signals.

Functions of Neuronal Cell Death

• Overproduction of neurons, followed by a subset dying.
• Death of neurons that make incorrect connections improves the accuracy of synaptic connections.
• New neurons creating more focused synapses.

Processes of Cell Death

• Apoptosis is an active, regulated process, removing damaged or unwanted cells.
• Necrosis is a passive, uncontrolled process.

What Causes Neurons to Die

• Genetic programming or preprogrammed cell death accounts for the death of some neurons.
• Competition for target-supplied neurotrophins is a major cause of neuronal death.
• The availability of neurotrophic factors regulates neural growth and survival.

Neurotrophins

• Types of neurotrophins include NGF, BDNF, GDNF, NT-3, NT-4/5, CNTF, and bFGF.
• These factors affect neuron development and survival in several ways.

Functions of Neurotrophins

• Promotion of neural growth and survival.
• Acting as axon guidance molecules.
• Assisting in synaptogenesis (the formation of synapses).
• Trigger apoptosis when absent; therefore, survival and development are dependent upon their presence.