Chapter 9 - Development of Nervous System

Zygote

Single cell, formed via fusion of ovum (egg) and a sperm

-divides to form two daughter cells, which then divide to form four, etc

Cells must differentiate, form at appropriate sites/organize into structures, and establish functional relations with other cells

Phases of Neural Development

1. Induction of Neural Plate

2. Neural Proliferation

3. Migration and Aggregation

4. Axon Growth and Synapse Formation

5. Neuron death and Synapse Rearrangement

Totipotent

A fertilized egg with the ability to develop into any class of cell in the body

-After new cells are created, they are no longer totipotent

Pluripotent - Developing cells with the ability to develop into many types of body cells (but not all)

-As the embryo develops and is more specialized, new cells are multipotent (develop into different cells of ONE class, such as different blood cells)

-Most cells are finally unipotent (only develop into one type)

Stem Cells

Totipotent, Pluripotent and Multipotent cells during early development are embryonic stem cells

-Two key properties of Stem Cells;

1. Unlimited capacity for self-renewal if maintained in appropriate cell culture (due to asymmetric cell division)

2. Ability of each stem cell to develop into many different kinds, likely governed via epigenetic mechanisms

Neural Plate

Three weeks after conception, is the tissue destined to develop into the nervous system

-Small patch of ectodermal tissue on the dorsal surface of the developing embryo

-Development of neural plate is induced by chemical signals from an area of the underlying the Mesoderm Layer - area consequently referred to as an organizer

Development of Neural Groove

Growing neural plate folds, forming the neural groove

-Lips of neural groove fuse to form the neural tube (inside eventually becomes the cerebral ventricles and spinal canal)

-After 40 days, three swellings are visible at the anterior end of the neural tube

Neural Proliferation

After formation of neural tube, cells of the tube proliferate (increase greatly in number)

-Most cell division in the neural tube occurs in the ventricular and subventricular zones (regions adjacent to the ventricles)

-Proliferation patterns are controlled by chemical signals from two organizer areas in the neural tube: Floor Plate (midline of the ventral surface of the tube) and the Roof Plate (midline of the dorsal surface of the tube)

Radial Glial Cells

Cells whose cell bodies lie either in the ventricular zone or subventricular zone

-Stem cells created in the developing neural tube

-Have long process that extends to outermost part of the developing neural tube

Migration

After cells have been created in the ventricular zone of neural tube, they migrate to the appropriate target location

-Cells are still immature (lacking processes like axons/dendrites)

Migration is governed by Time and Location

-Subtypes of neurons arise on precise/predictable schedules, then migrate together to particular destinations

Radial and Tangential Migration

Two types of cell migration in the developing neural tube:

Radial Migration - Proceeds from the ventricular zone in a straight line outward, towards the outer wall of the tube

Tangential Migration - Occurs at a right angle to radial migration (parallel to the Tube’s wall)

Somal Translocation

Mechanism by which developing cells migrate

-Developing cells have a process that extends from its cell body that explore the immediate environment

-Chemicals guide the movement of these processes (either attracting or repelling them)

-Once the process finds a suitable environment, cell body moves to the location via Radial or Tangential methods

Radial-Glia-Mediated Migration

Mechanism by which developing cells migration

-Developing cell uses long process that extends from each radial-glia cell (like a rope) which it pulls itself up and away from the ventricular zone

-Allows a cell to migrate ONLY IN RADIAL FASHION

Neural Crest

Structure situated dorsal to the neural tube, formed from cells that break off from the neural tube as it is being formed

-Neural Crest Cells develops into neurons and glial cells of the PNS and other cell types of the body

Aggregation

After developing neurons have migrated, they must align themselves with other developing neurons that have migrated to the same area to form structures of the nervous system

Mediated by Three Mechanisms:

1. Cell-Adhesion Moelcules (CAMs) - located on surface of neurons/cells, ability to recognize molecules on other cells and adhere to them

2. Gap Junctions - Play a role in aggregation/aspects of neural development by assisting in communication (via connexins)

3. Interaction of Glial Cells and Neurons

Axon Growth

After neurons have migrated into neural structures, axons/dendrites begin to grow

-Each growing tip of an axon or dendrite has a Growth Cone, extends and retracts fingerlike cytoplasmic extensions (Filopodia) that search for the correct routes

Pioneer Growth Cones - first growth cones to travel along a particular route, follow the correct trial by interacting with guidance molecules, following growth cones then follow routes by the pioneers

-Fasciculation - tendency of developing axons to grow along paths established by preceding axons

Synapse Formation

Synapses form at 700,000 synapses per second during neurodevelopment

-Spontaneous neurotransmitter release and and cell surface interactions between neurons are important in synapse formation

-Astrocytes also play a critical role

Synaptogenesis - Formation of new synapses

Neuron Death

Normal and important aspect of development, many more neurons are produced than required (thus, waves of large-scale neuron death occur), can be via;

Necrosis - Passive cell death (inadequate nutrition, etc)

-More dangerous (releasing contents into extracellular fluid may trigger inflammation)

Apoptosis - Active cell death (environmental triggers), removes excess neurons in a safe, neat and orderly way

-Safer, internal structures of the cell are cleaved apart and packaged into membranes before cells break apart

-Can lead to cancer if function is blocked, or neurodegenerative disease if too active

-Membrane packages attract microglia who engulf them

Triggers of Apoptosis

1. Some developing neurons are genetically programmed for an early death, then die in absence of obvious external stimulus

2. Some developing neurons die because they fail to obtain life-preserving chemicals supplied by their targets

-Most prominent class of these chemicals are neurotrophins (like Nerve Growth Factor and Brain-derived neurotrophic factor)

Synapse Rearrangement

During cell death, neurons with incorrect connections are more likely to die, resulting in massive rearrangement of synaptic corrections

-As they die, the space they leave vacant on postsynaptic membrane is filled by axon terminals of surviving neurons

-Microglia also play a vital role

Prenatal Brain Development Research

Period of development before birth

-Research has been asisted via 3D brain organoids in culture, new imaging techniques (functional connectivity), and development of transcriptomes (catalogue of all proteins transcribed in a particular cell)

Postnatal Growth of the Human Brain

Most growth occurs in the first year, continues into the third year

-Postnatal growth is a result of three kinds of growth; synaptogenesis, myelination of axons, and increase branching of dendrites

-Increase in synaptogenesis shortly after birth, differs based on the cortical region (ex; visual/auditory cortices have a major burst of synaptogenesis, while prefrontal cortex has a stable rate)

-Myelination increases speed of axonal conduction, myelination of sensory areas occurs in the first few months after birth, myelination of prefrontal cortex continues into adulthood

-Dendritic branching progresses from deeper to more superficial layers (inside-out)

Development of the Prefrontal Cortex

Most prolonged period of development of any brain region, responsible for the course of human cognitive development, cognitive functions include;

1. Working memory (keeping relevant information accessible while a task is completed)

2. Planning/carrying out sequence of actions

3. inhibiting responses inappropriate in certain contexts

4. Following rules of social behaviour

Preservation and Prefrontal Cortex Development

Preservation - tendency to continue making a formerly cortex response when it is currently incorrect

-Preservative errors occurring in infants between 7 and 12 months are due to a log in prefrontal cortex development