Development of the

CENTRAL NERVOUS SYSTEM

2022 MSPC 234
By
Frederick K. Addai, PhD, FWACM
Department of Anatomy, UGMS, KORLE-BU
ACCRA, GHANA
UGMS, Korle-Bu, Accra

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 • “The human brain has 100 billion
neurons, each neuron connected
to ten thousand other neurons.
Sitting on top of your shoulders is
Positive the most complicated object in
the known universe.”
Thought - --Michio Kaku (Born: January 24, 1947 [age 75 years])
- - American theoretical physicist, futurist, and
popularizer of science

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THIS LECTURE IS IN TWO PARTS
PART TWO
PART ONE
THE DEVELOPMENT OF
THE DEVELOPMENT OF THE SPINAL CORD AND
THE NEURAL TUBE & BRAIN
NEURAL TUBE DEFECTS

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Group Readiness Assessment Test (GRAT)
1. What is the primordium of 4. How many neurons are in
the brain and spinal cord the brain of a newborn
called? –Neural Tube human? 100 billion
2. Which primary germ layer
gives rise to primordium of 5. What is the weight of the
the brain & spinal cord? brain in an adult human?
Ectoderm 1,300 -1,400 g (2% bwt)
3. What is the weight of the
brain in a newborn human? 6. How many neurons are in
350-400g (10% bwt) the brain of an adult human?
86 billion?

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Interesting Comparative Anatomy
• What animal has the biggest
• What structural feature of the
brain? Sperm whale 7-9 kg;
human brain is superior to any
with bwt 45K kg, 0.02% bwt
other animal? Encephalization
quotient
• What animal has the highest • At what age does the human
brain to body ratio? Small brain reach maximum functional
ant (1:7) cf human 1:40 capacity??F-25 yrs. M-28 yrs.

Get my pdf writeup on Development of the Central Nervous System – It is FREE!!

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 Preview
1. A simple tubular structure
(Neural tube) is the primordium
of central nervous system
2. It arises from ectoderm as one
of the earliest organs to
commence development
3. Structural development is
completed about eight years
after birth
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4. Functional development
reaches maximum at age 25
in females and 28 in males
5. Billions of neurons die
throughout life, but does not
occur uniformly in every part
of the brain
6. Genes, lifestyle, and exposure
to toxins affect the rate of
neuronal senescence
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 PART ONE
DEVELOPMENT OF THE NEURAL
TUBE, & NEURAL TUBE DEFECTS
(NTDs)
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 THE NEURAL TUBE
• It commences development in a
gastrulating embryo
• It arises as one of three
structures formed from the
ectoderm
• The process by which it develops
is called NEURULATION

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 Neurulation
• Process by which three major structures arise in higher vertebrates:

1. the neural tube, which gives rise to the central nervous system.

2. the neural crest, which migrates away from the dorsal surface of
the neural tube and gives rise to a diverse set of cell types (see
Supplementary Resource Pdf for details)

3. the epidermis, which becomes the outer layer of skin.

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 GDFs of neurulation
• Bone Morphogenetic Protein 4
(BMP4) secreted by notochord binds
to all (surface) ectodermal cells
• BMP4 is inhibited by two sets of three
molecules
1. Noggin, Chordin, and Follistatin
produced by primitive node,
notochord, and prechordal
mesoderm.
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• Ectodermal cells inhibited by noggin,
chordin, and follistatin neuralize to
form forebrain and midbrain
2. WNT3a, FGF, and Retinoic acid
inhibit BMP4 in ectodermal cells
that form hindbrain and spinal cord
• These inhibitory signals are created
and emitted by the notochord in
interaction with paraxial mesoderm
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 Structural formation of neural tube
A scanning electron micrograph showing the
neural plate
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• Neural plate – appears in 3rd week
• Thickening of ectoderm inhibited
by 3 sets of GDFs
• If forms between the primitive
node and oro-pharyngeal
membrane
• It is broad cranially and narrows
caudally
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Signalling Molecules Involved (1)

• Ectodermal cells are induced to form neuroectoderm from a

variety of signals

• Ectoderm sends and receives signals of BMP4 (bone

morphogenetic protein)

• Ectodermal cells which receive BMP4 signal (without inhibition)

develop into epidermis

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Signalling Molecules Involved (2)
• Inhibitory signals chordin, • Inhibitory signals WNT3a,
noggin and follistatin bind FGF, and Retinoic acid bind to
receptors in ectodermal cells receptors in ectodermal cells
which become part of the to become part of the neural
neural plate, and will
become forebrain and plate, and will become
midbrain hindbrain and spinal cord

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 Neural tube formation
• Edges of neural plate undergo elevation
to give rise to a Neural groove bounded
by Neural Folds

Neural Groove

• Cells at crest (green in diagrams)of

neural folds differentiate and will not
participate in closure of the groove to
form a tube

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 Neural tube formation
• Neural groove continues to bend
superiorly until free edges meet and
fuse to for the Neural tube (purple
arrow)

• The neural tube detaches from the

surface ectoderm formed by cells whose
BMP4 was not inhibited – they form
Epidermis (blue arrow)

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Head- and Tail-fold
• The developing neural tube is associated
with the craniocaudal folding of the
embryo
• Thus, formation of Head fold and Tail fold
respectively
• The embryo consequently assumes a
curved shape by the 4th week

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Fusion of the Neural folds to form a tube
• The fusion of the neural folds
commences in the midline – at
the level of the 4th somite
• The region of initial closure is
the future junction b/n the
brain & Spinal cord
• The fusion first extends
cranially, and then caudally

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 Anterior & Posterior Neuropores

• There is a time when the fusing neural

tube is open at the cephalic and caudal
ends
• The Anterior (rostral) neuropore (brown
arrow in diagram) closes first on day 25 or
26
• The Posterior (caudal) neuropore (Blue
arrow in the diagram) closes 2 days later

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Neural tube defects (NTDs)
• Imperfect closure of the
neuropores results in gross
malformations of the brain and
spinal cord

• The variable anomalies are broadly

referred to as Neural Tube Defects
(NTDs)

• They are categorized by location

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 Craniorachischisis
• Failure of the neural tube to close through out the length
of the body

• Most severe type of NTD, in which almost the entire

brain and spinal cord remain open
•
• An affected foetus has both anencephaly and spina
bifida

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 Anencephaly
• Failure of the cranial neuropore to close
results in conditions called anencephaly.
• Viability of baby depends on the degree of
deformity.
• Characterized by variable degrees of
deformity with brain development.
• Ranges from total absence of brain and
head + neck to relatively minor defects.

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 Spina Bifida
• Failure of the caudal neuropore
closure results in conditions called
spina bifida

• Involves variable defects of the

arches of the vertebrae in affected
site

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 Spina bifida -prevention
• Maternal Folate (Vitamin B9)
deficiency is associated with
increased occurrence in babies

• Grand gravidity >35 years

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Spina Bifida variations
A. Occulta
B. SB with meningocoele
C. SB with meningomyocoele
D. SB with myeloschisis

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NTDs of the brain
A. Meroanencephaly
B. Meningo-encephalocoele
C. Microcephaly
D. Hydrocephalus

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 PART TWO
DEVELOPMENT OF THE SPINAL
CORD AND THE BRAIN

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How the Spinal Cord Develops from the Neural Tube
• The neural tube has a central
canal and a stratified epithelium

• The epithelium of the neural

tube consists of neuroectoderm

• The neuroectoderm is called the

matrix layer of the neural tube
A Cross-sectional diagram of the neural tube
showing its complex epithelium and central canal

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How the Spinal Cord Develops from the Neural Tube
• The neuroectoderm (Matrix
layer) proliferates producing
billions of cells (future neurons)

• Some cells migrate outside the

basement membrane of the
epithelium to become primitive
neurocytes
A Cross-sectional diagram of the neural tube
showing its complex epithelium and central canal

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 Formation of Spinal Cord from the Neural Tube
• The Cell bodies of the primitive
neurocytes form the Mantle
layer (future Grey matter)

• Cell processes extending from

primitive neurocytes form the
Marginal layer (future White
matter)
• After producing adequate numbers of neurocytes, the
neuroectoderm produces astrocytes and oligodendrocytes
• Finally, the neuroepithelium becomes simple cuboidal, and its
cells are called Ependyma
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Formation of spinal cord
• The accumulation of neurocytes in
the Mantle layer is not uniform
around the central canal of the
neural tube
• There are a pair of bilaterally Larger
inferior basal plates and a thin floor
plate
• There are a pair of bilaterally Smaller
superior alar plates and a thin roof
plate

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Formation of spinal cord
• With further development, the
neurocytes accumulated in the
basal plates develop into
multipolar neurons of the ventral
horn cells of the spinal cord

• For more information refer to my write-up

on the topic given to you as supplementary
resource material for this lecture

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Change in Length of the Spinal Cord with development

• At 3 months length of the cord is the

same as the vertebral column
• At birth spinal cord terminates at L3
• In adult spinal cord terminates at L1

• These changes have implications for the

level at which a needle may be safely
inserted during a lumbar tap to get CSF for
clinical investigations
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The Cauda equina (1)
• This structure is formed as a consequence
of the lag of the spinal cord behind the
growth in length of the vertebral column

• The spinal nerves from the lumbar

segments and below run in the vertebral
canal for variable distances before exiting
their corresponding intervertebral
foramena

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 The Cauda equina (2)

• When the spinal cord terminates, it

leaves obliquely coursing anterior and
posterior roots of the spinal nerves,
and the filum terminale

• Occupies the lower end of the

vertebral canal and collectively forms
the cauda equina
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 Development of brain

• Three brain vesicles form.

• From cranial to caudal –these
are
1. PROSENCEPHALON
2. MESENCEPHALON
3. RHOMBENCEPHALON

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 Prosencephalon
• By Week 5, Forms two structures –
Cranial Telencephalon, and
• Caudal Diencephalon
• Telencephalon develops two lateral
diverticula which become cerebral
hemispheres
• Diencephalon develops two smaller
diverticula as the Optic Vesicles

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 Rhombencephalon
• Forms cephalic Metencephalon and caudal Myelencephalon
• Ventral part of Metencephalon develops into the
Pons, whilst the dorsal part of Metencephalon
develops into cerebellum
• Pons gives origin to middle four cranial nerves; CNV.
CNVI, CNVII, and CNVIII
• Myelencephalon develops into the Medulla
Oblongata which is continuous with the spinal cord
• Medulla gives origin to last four cranial nerves; CNIX,
CNX, CNXI (cranial part), and CNXII

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BRAIN DEVELOPMENT PROCESSES

• There are five basic processes that make up brain

development

• Many of these processes begin before birth, during the

prenatal period

• Most are not complete until late adolescence

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 THE FIVE BASIC BRAIN DEVELOPMENT
PROCESSES
1. Neurogenesis
2. Neural migration
3. Myelination
4. Synaptogenesis
5. Pruning

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 Neurogenesis
• The process of forming neurons
• This is the first process to
occur in brain development,
and is completed before birth
• 100 billion neurons are
produced

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Neural migration
• The process of organizing the brain by • Neural
moving neurons to specific areas based on migration uses
the functions these cells will perform neuroglial
• processes as
• Migration begins prenatally, but continues scaffolding
for at least 8 to 10 months after a baby is
born

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 Myelination

• The process of coating the axon of

each neuron with a fatty coating called• Myelination begins in the brain
myelin stem and cerebellum before birth
but is not completed in the frontal
• Myelin protects the neuron and helps cortex until late in adolescence
it to conduct signals or impulses more
efficiently • Breast feeding contributes to
more rapid myelination in the brain
• In the brain oligodendrocytes are
responsible for myelination, whilst
Schwann cells myelinate axons of
peripheral nerves
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 Synaptogenesis
• The process of forming networks of
specialized connections in the brain
• Synapses begin forming prenatally, but the
process continues throughout life
• Synaptogenesis is facilitated by exogenous
cues including playing classical music,
reading, and peaceful surroundings

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 Pruning
• The process of weeding out
underutilized connections and
strengthening the more frequently
utilized ones based on the baby or
child's experiences
• Some pruning begins very early in
development, but the most rapid
pruning happens between about age
3 and age 16
• Different areas of the brain
undergo pruning during
different sensitive periods
• Periods Such as infancy,
adolescence, and
advanced age (>90 years)
are characterized by
specific localized pruning

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 Summary -1
• Neural tube commences development
rd
from 3 wk. just as gastrulation is being each
completed.
• Ectodermal –mesenchymal interactions
via GDFs result in formation of neural
tube, neural crest, and epidermis.
• Cranial part of NT forms 3 vesicles.
• First and third vesicles form two structures
• Cranial part of third vesicle forms pons
anteriorly, and cerebellum posteriorly
• Caudal part of 3rd brain vesicle forms
medulla oblongata contiguous with Spinal
cord

• Caudal part of NT forms spinal cord

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 Summary-2
• Forebrain and midbrain are
formed by cells that bind Chordin,
Noggin, and Follistatin (3 BMP4-
inhibitory GDFs acting together)
• Hindbrain and spinal cord are
formed by cells that bind WNT3a,
FGF, and Retinoic acid (another
set of BMP4-inhibitory GDFs
acting together)
• First and third brain vesicles form
two structures each
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• 2nd brain vesicle –midbrain- remains
relatively unchanged
• Cranial part of forebrain forms
telencephalon which becomes
cerebral hemispheres
• Caudal part of forebrain forms
diencephalon
• Developmental processes of the brain
are; neurogenesis, neural migration,
myelination, synaptogenesis, and
pruning
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THE THE END

•HAVE A GREAT DAY!

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