DEVELOPMENT OF THE NERVOUS SYSTEM:Stages of development, Neurulation

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Neurological Basis of Behavior (PSY - 610)

Lesson19

DEVELOPMENT OF THE NERVOUS SYSTEM

Objective

To familiarize the students with:

· Various stages of neuronal development.

· Development of the brain: from the fertilization to the various developmental stages in-utero,

and postnatally.

· Cell differtiation, determination migration, (inside-out), cell competition, Cell death, growth

Cones, Nerve growth Factor and its role, Influences in growth and development of the brain

Once induction of the ectodermal layer by the mesodermal tissue has taken place, the cells start

differentiating as their direction of growth is determined by the induction. The three cell layers would

develop in different direction after the signal has taken place. The initial division of cells is

differentiated into different organs (heart, kidney, brain, stomach) this change has been induced by the

notochord which ahs thus determined the fates of cells/layers

Stages of development

There are several distinct and measurable stages of development of the brain which takes place.

Attachment of mesodermal tissue to ectodermal tissue leads to the formation of the notochord.

The notochord is the strip at the center of the upper surface of the ectodermal layer.

The neural plate is formed from this tissue and this line in the center grows as the plate grows.

A bulb like head end forms at one end to eventually form the forebrain and eye field/eye cups

area around the 17th day of intrauterine life. If the bulbous end is cut, it would quickly replace

itself. The cells are still rapidly dividing

The neural plate starts becoming longer and broader-growth in both directions (as the cells are

still dividing and multiplying at an extremely rapid rate)

On the18th day there is thickening of the outside ends. This leads to rising of ends and

deepening of the center. The sides rise joining in the middle. Thus, the rising of the plates form

a groove, this is called the neural groove. The neural groove deepens as the sides rise higher

and higher (remember, there is rapid cell growth and multiplication taking place).

Neurological Basis of Behavior (PSY - 610)

Neurulation

Neural tube (rapid cell multiplication and division), the tube folds and becomes tubular this is

when the primary neurulation takes place. The brain and spinal cord are formed at this stage.

On the 21st day, the fusion of the tube takes place and little groups of cells break away to form

bunch on both sides. These are called somites and extend in both directions (somites: bodies of

cells in the middle/top) to form the neural crest. These develop into the peripheral Nervous

system and the ganglionic system. The inside of this tube, the neural canal, is empty at this

stage.

The neural canal remains empty as the ventricular zone, where the next phase of development

will take place. Secondary neurulation: During the process of secondary neurulation (forming

of the neural systems) the tail end part of spinal cord is formed

The closure of the tube is simultaneous and inside cells starts dividing and multiplying, growing within

the tube. The cells inside increase in number rapidly, as cell division takes place in the ventricular zone.

Internal part of the tube consists of single layers of cells which keep multiplying and increasing in

number and as they increase in number the cells start moving out (The interesting question is who tells

them where to go, and where do they go? Does the region get crowded??). This is the phase when Cell

Migration takes place

Cell migration: it is an inside-out process, cells move form the inside of the tube towards outside. The

growing cells then form three layers: internal, middle, cell free:

1. The Internal layer: The inner most layer has cells which are still dividing

2. The Middle layer: Consists of cell bodies which eventually form grey matter. These cells do

not divide after this, these are the same cells found in the adult brain.

3. Cell free zone: This contains the fibre processes of the first two layers and as yet empty of

cells. The migration is still taking place. Once cells reach their destination they grow dendrites

and axons to reach out to meet other cells. Cells sprout growth cones for the axons and

dendrites, which lead the cells to grow to and to develop synapse.

Neural crests are forming ganglia, inputs into spatial column and outwards, Optic stalk grows out of

diencephalon to form eye cup- eye cups induce formation of lens from overlapping ectodermal

tissue. The frontal the eyecups: retina forms as an invagination of the bulging optic vesicle:

ganglionic cells first, and then bipolars, and photorecpetors last: eye born directly from brain tissue!

Common substance in both

Formation of the brain:

Forebrain, mid brain, hind brain: On the 24th day intrauterine, the head end part of neural tube

forms three bulbs. These three bulbs would form the forebrain, midbrain, hind brain (The question

is how do the cells know and the areas know that they are going to be the in front or middle or

back?) The front most becomes the forebrain, and the end toward the tail becomes the hind brain.

The hind brain connects with the spinal cord. At this point all three bulbs are not differentiated.

These are exactly the same. (How do they become different?). In the same manner as in the first

stages, each area depends on the other to be stimulated and through this interaction they

differentiate. At the stage also the surrounding area induces differentiation. The environmental

influences are important at every stage.

What if the three bulbs cut and rotated, always the bulb in the front forms the forebrain and the

middle, the mid brain and the last part forms the hind brain. The position determines direction of

Neurological Basis of Behavior (PSY - 610)

development! The same cells develop into different regions if their locations are changed

(environmental change!). At this stage cell division is rapid, and the neurons and glial cells are

forming. The migrating cells unite to form groups of neurons. Nuclei are forming as a result of rapid

proliferation of nerve fibre tracts and connections.

· Cell division is rapid:

· Migrating cells unite to form groups of nuclei\nuclei form connections

· Rapid proliferation of fibre tracts and connections

· Formation of the ganglionic systems from the neural crests, inputs into the spinal column and

outwards

· Optic stalk grows out of the diencephalons to form the eye cup ( the eye is formed from the

same tissue as the brain, eye has similarities with the brain)

· Eye cups induce formation of the lens from overlapping ectodermal tissue

Concepts

Regulation: If cells keep growing, connections expanding then how does it stop- who controls the

development, differentiation, and migration etc.

Self regulating: This is a process regulated by itself. A) Muscles move without the sensory input or

stimulation b) nuclei develop even if isolated from the organs, if we denervate (cut the nerves).

Cells proliferate at more than 40 times the normal adult brain. What happen that cells size reduces?

Cell proliferation (increases in number), cell migration (cells travel to their destinations form inside

toward the outside), maturation (developing extensions) interconnections formed (forming connections

with other cells); cell death (cells die off) is taking place.

Cell proliferation: Cells are dividing, spreading and increasing in number. Specific parts of the brain

begin to differentiate. Small piece of ectodermal tissue removed defect replaced by proliferation of

neighboring cells, however if surgery is done later, then it would remain as a permanent deficit. The cell

growth is in extreme density in ventricular zone. Cell growth much more than required about 1 ½ times

more than adult brain then cell death takes place and has to follow some principles.

Maximal cell division is taking place at this stage and neurons are being formed at 20.000 neurons per

minute.

Growth spurt: This is time when maximal cells are being formed, connections being formed and

systems of brain areas organized. This is between the 10-18th week of gestation. This is the time when

the brain cells of the growing embryo are sensitive to radiation, chromosomal anomalies, viral infections

(measles etc.). The fetus is born with defects such as mental retardation and blindness. The sensitivity of

the fetus and the newborn to other effects are from the 30th week- 2nd year post partum. The effects of

malnutrition on cell size, brain cell connections and myelination are irreversible.

Cell Migration: Cells migrate towards periphery from the inner core of the ventricular zone. The

principle of inside out migration is followed here. There is formation of radial glial fibres on which

cells travel from the periventricular zone. These form the transport system on which neurons travel!

These cells move up to the different cortical regions which would eventually form the 6 layers of the

cortex, some remain.

Radial Glial: cells attach on both sides, neurons move up, some slow, some fast... those which are fast

arrive earlier and form connections with other neurons. Once they form connections they survive. The

sooner the connections are formed, the greater chances of surviving.

Neurological Basis of Behavior (PSY - 610)

Cellular maturation.

This has four stages

a) The development of outgrowth and elongation of axons

b) Dendritic process emerging out of the cell body

c) Biochemical properties appropriate to the location and function of the location to which the cell

would stay

d) Development of synaptic connection.

The axons grow out of neurons first and these have a growth cone (a specialized structure with filopedia

cytoplasmic extensions--feelers needed for movement which lie on the growing processes). This is

affected by the Growth Factors, the active factors being the Nerve Growth Factor (NGF) in the growing

nervous system and factors that maintain metabolism of neurons (tropic factors). This is planned for a

specific site and target.

Dendrites develop after neurons/axons. Immediately upon reaching their destination neurons attach to

the site after detaching from the transport radial glial, and send out projections. If the neurons cannot

travel, they cannot compete, they would not survive. If they cannot from connections, they cannot

compete, they would die. In order to survive, cells sprout more extensions and form more connections.

This increases the cell's ability to compete for connections. If the connections not formed, cells will not

be able to survive. Only those cells survive which have successfully formed connections and would now

be able to continue receiving the NGF

Cell Aggregation: Cells make their way to the area in which they will function as adults using cell

adhesion molecules (CAMs). These cell adhesion molecules are formed on the surface of neurons and

other cells. These also give the cell ability to recognize the molecules and surfaces. Cells form

alignment in precision with other cells in the region. The question is how it is done. There is an intricate

programming which is still under study.

Fate Mapping: researches such as Pasko Rakic sued the fate mapping procedures. This involves

injecting labelled substance in the growing brain at various embryonic ages and following the migration

of the neurons later to see where they end up. These studies have shown that a) Regional specialization

of areas and neurons appears early on in development, b) The deeper cortical layers generate first and

most superficial layers are formed last c) Inside-Out migration: The migration is at a fast pace, the cells

migrate to the inner layers first. Neurons of the outer layers formed later must migrate through the

earlier formed layers to eventually arrive at their destination, d) In the development and growth

principles i) large cells develop before small ii) motor cells develop before sensory neurons and iii)

neurons develop before the glial cells.

Thus, we have seen an intricate relationship of genetic and biological programming with environmental

stimulation in the development of the brain. Even though the paths of development are well laid out,

stimulation is important for neurons to continue moving, developing and surviving.

References

1. Kalat J.W (1998) Biological Psychology Brooks/ Cole Publishing

2. Carlson N.R. (2005) Foundations of Physiological Psychology Allyn and Bacon, Boston

3. Pinel, John P.J. (2003) Biopsychology (5th edition) Allyn and Bacon Singapore

4 Bloom F, Nelson and Lazerson (2001), Behavioral Neuroscience: Brain, Mind and Behaviors (3rd

edition) Worth Publishers New York

5. Bridgeman, B (1988) The Biology of Behaviour and Mind. John Wiley and Sons New York

6. Brown,T.S. And Wallace. (1980) P.M Physiological Psychology

Academic Press New York

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