PSYC Textbook notes from after the second midterm
Chapter 9- Development of the Nervous System
The brain is not static, it is plastic (changeable) and it continuously changes in response to its genetic programs
and environment. Neural development begins with a single fertilized egg cell and ends with a functional adult
9.1 Phases of Neurodevelopment
In the beginning, there is a zygote- a single cell formed by the amalgamation of an ovum and a sperm. The zygote
divides to form two daughter cells These two divide to form four, etc until a mature organism is produced.
Three things must occur
1. Cells must differentiate; some must be muscle, some multipolar neurons, some glial cells etc
2. Cells must make their way to approptiate sites and align themselves with the cells around them to form
3. Cells must establish appropriate functional relations with other cells
Development of neurons accomplish these in five phases
1. Induction of the neural plate
2. Neural proliferation
3. Migration and aggregation
4. Axon growth and synapse formation
5. Death and synapse rearrangement
Induction of the Neural Plate
Three weeks after conception, the tissue that is destined to develop into the human nervous system becomes
recognizable as the neural plate- a small patch of ectodermal tissue on the dorsal surface of the developing
embryo. The ectoderm is the outermost of the three layers of embryonic cells: ectoderm, mesorderm, endoderm.
The development of the neural plate is the first major stage and it is induced by chemical signals from an area of
underlying mesoderm layer- an area also know as the organizer. Tissue taken from this layer of one embryo and
implanted beneath the ventral ectoderm of another embryo induces the development of an extra neural plate on
the ventral surface of the host. Once the neural plate becomes visible a change occurs.
The earliest human embryo cells are totipotent- they have the ability to develop into any type of cell in the body if
transplanted to the appropriate site. As the embryo develops, more specified. Its cells lose some of their potential
to become different kinds of cells. Each cell of the neural plate has the potential to develop into most types of
mature nervous system cell, but not into others (multipotent).
The cells of the neural plate are often reffered to as embryonic stem cells. Stem cells are cells that 1) have
seemingly unlimited capacity of self renewal if maintained in appropriate cell culture and 2) have the ability to
develop into different types of mature cells. However, as the neural plate develops into the neural tube, some of
its cells become specified as future glial cells of various types and others become specified as future neurons of
various types. First stem cells to develop, others develop later.
Unlimited capacity for renewal because when a stem cell divides, two different daughter cells are created: one
eventually develops into another stem cell. Keep dividing forever through mitosis, but eventually errors
accumulate that disrupt the process thus they do not last forever.
The neural plate folds to form the neural groove then the lips of the neural groove fuse to form the neural tube.
The inside of the neural tube eventually becomes the cerebral ventricles and spinal canal. By 40 days after conception, three swellings are visible at the anterior end of the human neural tube; the swellings develop into
forebrain, midbrain and hindbrain.
Once the lips of the neural groove have fused to create the neural tube, the cells of the tube begin to proliferate
(increase in number). This does not occur at once or equally in all parts of the tube. Most cell division occurs in the
ventricular zone (adjacent to the ventricle-fluid filled portion in tube). Proliferation is controlled by floor (midline
of anterior) and roof plate (midline of dorsal surface).
Migration and Aggregation
Migration: once created, cells migrate to the target location. During migration, cells are still immature, lacking
processes (axons and dendrites) that characterize mature neurons. In a given region, subtypes of neurons arise on
a precise and predictable schedule and migrate together.
Cell migration in the developing neural tube is considered to be of 2 kinds: radial migration proceeds from the
ventricular zone in a straight line outward toward the outer wall of the tube. Tangential migration occurs at a
right angle to radial, parallel to tubes walls. Most cells use both.
Two ways to migrate. Somal translocation an extension grows from the developing cell in the direction of
migration and explores the environment for attractive and repulsive cues as it grows. Cell body then moves into
and along the extending process and trailing processes are retracted (grab and pull).
Glia mediated migration once the period of neural proliferation is started and the walls of the neural tube are
thickening, a temporary network of glial cells (radial glial cells), appears in the developing neural tube.At this
point, most cells use this migration (radial). Inside out pattern because each wave of cortical cells migrate through
formed lower layers of cortex before reaching destination. Many cortical cells engage in long tangential migrations
to reach their final destinations, and the patterns of proliferation and migration are different for different areas of
the cortex. (Only radial while somal is radial and tangential). The neural crest is a structure that is situated just dorsal to the neural tube. It is formed from cells that break off
from the neural tube as it is formed. Neural crest cells develop into neurons and glial cells of the PNS and thus
many migrate over long distances.
Aggregation: once they have migrated, they need to align themselves with other migrated developing neurons of
same area and structure. This is aggregation. Both migration and aggregation are thought to be mediated by cell-
adhesion molecules (CAMs). These are located on the surfaces of neurons and other cells. They have the ability to
recognize molecules on other cells and adhere to them. Elimination of on type of CAM in a knockout mouse has a
devastating effect on brain development. This suggests that abnormalities of CAM function may be causal factors
in some neurological disorders.
Gap junctions between adjacent cells are prevalent during brain development (not as wide as synapses, points of
connection between two neurons, and bridged by narrow connexins through which cells can exchange cytoplasm).
Possibly play role in aggregation.
Axon Growth and Synapse Formation
Axon Growth: Once migrated and aggregated into neural structures, axons and dendrites begin to grow from
them. For the nervous system to function, these projections must grow to appropriate targets. At each growing tip
of an axon or dendrite is a structure called growth cone which extends and refracts fingerlike cytoplasmic
additions called filopodia. Roger sperry did an experiment to demonstrate that axons are capable of precise
growth. In one study, he cut the optic nerves of frogs, rotated their eyes 180 degrees and waited for the axons of
the retinal ganglion cells, which compose the optic nerve, to regenerate (mammals cannot regenerate retinal
ganglion cells). He dangled a lure behind the frogs, they struck forward, thus indicating that their visual world has
also been rotated 180 degrees. Frogs whose eyes had been rotated, but whose optic nerves had not been cut,
responded in exactly the same way. This strong evidence that each retinal ganglion cell had grown back to the
same point of the optic tectum (superior colliculus in mammals) to which it had originally been connected. (MORE
ON THIS EXPERIMENT IN NOTES)
On this study, Sperry proposed the chemoaffinity hypothesis of axonal development. He hypothesized that each
postsynaptic surface in the nervous system release a specific chemical label and that each growing axon is
attracted by the label to its postsynaptic target during neural development and regeneration. This hypothesis fails
to account for the discovery that some growing axons follow the same circuitous route to reach their target in
every member of a species, rather than growing directly to it.
New hypothesis says that a growing axon is not attracted to its target by a specific attractant released by the
target and that instead, growth cones are influenced by a series of chemical signals along the route. These
guidance molecules are similar to those that guide neural migration in the sense that some attract and others
repel the growing axon.
Pioneer growth cones- the first growth cones to travel along a particular route in a developing nervous system-
are presumed to follow the correct trail by interacting with guidance molecules along the route. Then, subsequent
growth cones embark on the same journey follow the routes blazed by the pioneers. The tendency of developing
axons to grow along the paths established by preceeding axons is fasciculation.
Topographic gradient hypothesis- explains accurate axonal growth involving topographic mapping in the
developing brain. According to it, axons growing from one topographic surface (ie retina) to another (ie optic
tectum) are guided to specific targets that are arranged on the terminal surface In the same way as the axons’ cell
bodies are arranged on the original surface. Key part of this hypothesis is that the growing axons are guided to
their destinations by two intersecting signal gradients. Synapse Formation
Once axons have reached their initended sites, they must establish an appropriate pattern of synapses. A single
neuron can grow an axon on its own, but it takes coordinated activity in at least two neurons to create a synapse
between them. Synaptogenesis is the formation of new synapses and depends on the presence of glial cells,
especially astrocytes. Developing neurons need high levels of cholesterol during synapse formation, and the extra
cholesterol is supplied by astrocytes. Astrocytes also transfer and store information supplied by neurons.
Although the brain must be wired according to a specific plan in order to function, in vitro studies suggest that any
type of neuron will form synapses with any other type. However, once established, synapses that do not function
appropriately tend to be eliminated.
Normal and important role in neurodevelopment. 50% more neurons are produced than neeed, and large scale
neuron death occurs in waves in various parts of the brain throughout development. Cell death during
development is usually active. Genetic programs inside neurons are triggered, causing them to actively commit
suicide. Passive cell death= necrosis (die when not enough nutrition), active= apoptosis.
Apoptosis is safer than necrosis. Necrotic cells break apart and spill their contents into extracellular fluid and it can
be harmful (inflammation). In apoptotic cell death, DNA and other internal structures are cleaved apart and
packaged in membranes before the cell breaks apart. These membrane containing molecules that attract
scavenger microglia and other molecules that prevent inflammation. Apoptosis removes excess neurons in a safe,
clean orderly way. Dark side: if genetic programs for apoptotic cell death are blocked, this can lead to cancer; if the
programs are innapropriately activated, lead to neurodegenerative disease.
Two kinds of apoptosis triggers: (1) some developing neurons appear to be genetically programmed for an early
death- once they have fulfilled their functions, groups of neurons die together in the absence of any obvious
external stimulus. (2) some developing neurons seem to die because they fail to obtain life preserving chemicals
that are supplied by their targets. Evidence that life preserving chemicals are supplied to developing neurons by
their postsynaptic target comes from two observations: (1) grafting an extra target structure (ie extra limb) to an
embryo before synaptogenesis reduces the death of neurons growing into the area and destroying some of the
neurons growing into an area before th period of cell death increases the survival rate of the remaining neurons.
Several life preserving chemicals: Neurotrophins such as nerve growth factor (NGF). Neurotrophins promote the
growth and survival of neurons, function as axon guidance molecules and stimulate synaptogenesi