Development of Nervous System ( Embryological Development)

Neural Development is one of the easiest systems to begin with and the last one to be
completed after birth. This development generates the most complex structure within the
embryo and the long time period of development.
The early nervous system (central nervous system) begins as a simple “neural plate” which then
folds to become grove and these tubes which are initially open at both ends.
Failure of these opening to close down contributes a major class of abnormalities (neural tube
defects)

“Neurulation”​ is a process of formation of a “neural tube” from Ectoderm. As we know that

when sperm fertilizes the egg, the zygote then further divides and develops in Blastula.
Next cell differentiation begins into 3 layers of Gastrula (Blastula changes into Gastrula)
These three layers are known:
1.) Ectoderm​ (outer layer)
2.) Mesoderm​ (middle layer)
3.) Endoderm​ (inner layer)

The Ectoderm of Gastrula develops into skin, sense organs, and nervous system.
Gastrula Mesoderm develops into muscles, bones, tendons, heart, and blood vessels.
Endoderm develops into the gastrointestinal system, liver, and lungs.
After Gastrulation the notochord (In mesoderm, forms as a result of cell differentiation), a
flexible, rod-shaped body that runs along the back of the embryo.
During the third week of pregnancy (Gestation) the notochord sends signals to the overlying
Ectoderm, asking/inducing the ectoderm to become “Neuroectoderm”.
This process results in making a strip of “neural plate” and hence is the origin of the entire
nervous system. The neural plate folds outwards to form the neural groove.
In the future, the neck region of the fetus, the neural folds of this groove closes off and creates
the neural tube.
Within the neural tube stems cells generate the 2 major classes of cells which makes the
majority classes of cells which in turn makes the majority of the nervous system. Special neural
cells form and migrate throughout the embryo to form the beginnings of nerves. Baby’s nervous
system is made up of millions of neurons.

How Neurons are formed during fetal development.

Four processes underlie changes in the nervous system during fetal life and hence results in the
formation of neurons.
Neural Development​ is a biological process by which neurons are produced.
The process includes:
1.) Cell proliferation
2.) Differentiation
3.) Migration
4.) Axon Myelination
5.) Synapse Formation

All these 5 processes occur at different times, at different rates, and in different parts of the
neural tube.

Cell Proliferation:​ ​Production of neurons is known as cell proliferation.​ Neurons are produced
initially as a single layer of cells which forms along the inner surface of the neural tube. All
ectoderm cells in embryos have the ability to develop into neural tissues, but only those
ectoderm cells which are close to the notochord shall do so. In mammals, the process of
forming neurons in the ventricular layer continues until birth.

Differentiation of Neurons:​ ​The notochord forms and releases chemicals into the overlying
ectoderm, causing those cells to differentiate into neurons.
Neural tube lies above the notochord and it will give rise to all the nervous tissues in the body
including sensory neurons in toes, fingers, spinal cord, and optic neurons from the eye.

A group of cells called neural crest cells migrate out of the neural tube and travel to different
parts of the developing embryo. These cells will develop into facial bones, tissues covering the
brain , and neuronal support cells called Glial cells in the Peripheral Nervous System.

This differentiation process is clearly illustrated by two best known chemicals released by the
Notochord.
1.) Sonic hedgehog
2.) BMP (Bone Morphogenic Protein.)

High concentration of sonic hedgehog in a cell causes it to develop into a motor neuron
whereas high concentration of BMP causes cells to develop into sensory neurons.
Sonic hedgehog is released from the dorsal (towards the back)
BMP from ventral region (towards the front)

Cell Migration:​ Many undifferentiated pre-neuronal cells are born near the ventricles
(fluid-filled) spaces located in the centre of the brain, and then migrate to another region.
Neuronal migration is pretty dependent on chemical guidance cues from the tissues through
which they grow and partly on supporting cells along which migrating neurons can travel.
One example of this migration is a sensory neuron in a 7 foot tall person; the sensory neuron
has its cell body in the spinal cord but must extend an axon to the big toe nearly 3 and a half
feet away. Chemicals in the back, thigh, leg, and foot tell the neuron in which direction to grow.
Neuronal migration

It is the method by which neurons travel from their origin or birthplace to their final position in the
brain.
There are several ways of migration such as:
1.)Radial Migration
2.)Axophilic
3.)Tangential

It is important to note that nerve cells do not move in a haphazard manner. Many studies show
that nerve cells move from the inner to outer surface of the emerging nervous system and get
settled to their destination.

Later Developmental Processes:​ Between birth and maturity the human brain increases four
folds (4 times) in weight and size; due to changes from infancy to adulthood, let us consider four
types of changes at a cellular level that characterize brain development during early postnatal
period.

Myelination:

The development of the sheath around axons- a process called myelination changes the rate at
which axons conduct messages and have a strong impact on the behavior. It affects the
temporal order of events in the nervous system.
In humans the most intense phase of myelination occurs shortly after birth. The first nerve tract
in the human nervous system to become myelinated is found in the spinal cord.
Myelinizatoin then spreads successively into the hindbrain, midbrain, and forebrain.
Within the cerebral cortex, sensory zones myelinate before motor zones, correspondingly,
sensory functions mature before motor functions.

Formation of Synapses and Dendrites:

From birth to maturity the biggest changes in the neurons takes place in the form of branches
and connections amongst neurons, and also increases in the length of dendrites. At the tips of
Dendrites there are Growth cones which are swollen ends from which extensions arise. The
elongation of dendrites may continue throughout life. To support the extending dendrites the
neuron's body must increase in size.
Production of neurons after birth:

Many investigators believed that mammals at birth have all the nerve cells they will ever have.
Postnatal growth in the brain entirely in terms of growth in the size of neurons and addition of
Glial cells. Some neurons are added for some period following birth.
Few regions like subventricular zones in which mitotic divisions remain evident after birth.

Formation of Glial Cells:

Glial cells develop as supporting cells.

They continue to be added up throughout life.
After birth, mainly the production of proliferation of Glial cells occurs.
The hollow interior of the tube is known as a neural canal. At the both upper and lower end of
this neural tube lies the opinions as neuropores.
These neuropores close off by the end of the 4th week of gestation.
To each side, left and right of the neural plate there are neural crests which later develop into
peripheral nervous systems.
The cells in the neural tube and crest then differentiate into glial cells.

Formation of Brain:

Late in the 4th week the neural tube flexes at the place of the midbrain, the upper part of it
becomes the future forebrain. Mesencephalon is the future hindbrain Rhombencephalon.
The optical vesicles (which later will become) optic nerve, (Iris and retina) forms at the base of
the prosencephalon.
During the 5th week the prosencephalon expands to form the cerebral hemisphere
telencephalon and the basal part becomes diencephalon.
The rhombencephalon (hindbrain) expands posterior and forms the 4th ventricle of brain, pons ,
and cerebellum form in the upper part of the rhombencephalon whilst medulla forms in the
lower.

Formation of Spinal cord:

Spinal cord forms from the lower part of the neural tube.
Walls of the neural tube consist of neuroepithelial cells which differentiate into neuroblasts
which form grey matter and nerve fibres emerge from these neuroblasts which form white matter
marginal layers.
Embryology of The Nervous System:

For some very simple animals, the entire nervous system is completely hard-wired. It is
precisely determined by a blueprint in the genes. The nematode Caenorhabditis elegan for
example contains precisely 302 neurons and about 7,000 synapses with highly stereotyped
connections. But even in the development of C. elegans from a single cell, the descendant cells
do not develop as autonomous units. Rather, developing cells interact so that some cells
specifically influence the development of others.

The development of most animals from a zygote follows a specific sequence of events; divisions
of the zygote into many undifferentiated blastula cells, the formation of three progenitor cell
layers in a gastrula, differentiation, and reorganization of the progenitor cells into tissues and
organs, growth and maturation, and then programmed aging.

The zygote typically develops into a blastula by a series of divisions that leaves the many-celled
blastula as large as the original zygote. Like the zygote, each blastula cell has the capability of
developing into a unique individual- and this is the basis of identical twins, triplets, etc. Human
embryos that are frozen in liquid nitrogen are frozen as 8 celled blastulas. Cell differentiation
begins with the emergence of the cells in the three primordial layers of the gastrula: the
ectoderm (outer layers, the mesoderm (middle layer) and the endoderm (inner layer).

Roughly speaking, the gastrula ectoderm develops into the skin, the sense organs, and the
nervous system. The mesoderm develops into the muscles, bones, tendons, heart and blood
vessels. The endoderm develops into the gastrointestinal system, the liver and lungs.
Psychologist W.H Sheldon attempted to classify human personality types as being dominated
by these germ layers. Ectomorphs he characterized as ‘skinny’ introverted, cerebral, and
hypersensitive. Mesomorphs he described as muscular and athletic. Endomorphs he regarded
to be rotund and visceral (polarized toward gaiety or depression). Perhaps the greatest value of
this classification scheme is that it is of assistance in remembering the germ layers.

The progenitor cells for all the neurons and glial cells of the central nervous system begin as a
further differentiation of ectoderm cells into a layer known as the neural plate. Neural plate
formation is induced by chemical signals from the mesoderm (evidently peptides with molecular
weight less than 1,000). The neural plate folds and differentiates into neural crest cells and
neural tubes. The neural crest cells become the peripheral nervous system, whereas the neural
tube becomes the central nervous system. Cells in both structures differentiate into glial cells of
various types- as well as into immature neurons which migrate, grow axons and dendrites, form
synapses and mature.

In the nucleus of all cells of the human body are 23 chromosomes containing all human genes
(the human genome) in the form of DNA. The difference between a zygote, a mesoderm cell, a
neuron, a kidney cell and a muscle cell lines in the parts of the chromosomes with DNA
exposed.

Early in an embryo's development, a strip of specialized cells called the notochord induces the
cells of the ectoderm directly above it to become the primitive nervous system. The
neuroepithelium then wrinkles and folds over. As the tips of the folds fuse together, a hollow
tube (the neural tube) forms- the precursor of the brain and spinal cord. Meanwhile, the
ectoderm and endoderm continue to curve around and fuse beneath the embryo to create the
body cavity, completing the transformation of the embryo from a flattened disk to a
three-dimensional body. Cells originating from the fused tips of the neuroectoderm (neural crest
cells) migrate to various locations throughout the embryo, where they will initiate the
development of diverse body structures. Researchers investigating fetal alcohol syndrome have
extensively studied neural crest cells, because they are particularly sensitive to alcohol-induced
injury and cell death.