The development of the CNS is a fascinating process that occurs during embryonic development and continues into early childhood. Disruptions or abnormalities during this process can lead to a wide range of neurological disorders and developmental disabilities. Understanding the mechanisms underlying CNS development is critical for advancing our knowledge of brain development and for developing new therapies for neurological disorders.

1. Dr / Ahmed Salah Ashour(Ph.D.)
Associate professor of human anatomy
Dr.Ahmedashour@gmu.ac.ae
USMLE Clinical Anatomy

2. Case report

3. A term female infant of 9 days old was
born with a big head. There was no history
of a decrease or increase in size. She had
neither convulsions nor fever.
No abnormalities were noted except for
the mucous vaginal discharge which is not
unusual for a female baby.
On examination, anterior and posterior
fontanelle had widen.
Anthropometric measurement;
Occipitofrontal Circumference 49.5cm,
(normal 32-35cm conclusion,
Hydrocephalus) Length 49cm.

4. Cranial US, bilateral ventriculomegally
The diagnosis was made after, cranial ultrasound scan (US) revealing huge
hydrocephalus with bilateral ventriculomegally merging into one probably due to
atresia of the aqueduct of Sylvius.

5. The baby kept warm with daily monitor
of the respiratory rate, heart rate,
temperature, Hypoxic Ischaemic
Encephalopathy.
The treatment of hydrocephalus was
done as a shunt of the CSF fluid to
peritoneum (ventrricoloperitoneal
shunting).

6. CNS
DEVELOPMENT

7. ILOs
• Understanding the stages of CNS development
• Recognizing the key cellular mechanisms involved in CNS development,
such as neurogenesis, migration, and synaptogenesis.
• Explaining the significance of critical periods in CNS development for
establishing neural circuits and functions.
• Understanding the implications of disruptions in CNS development for
neurological disorders and developmental disabilities.
• Applying knowledge of CNS development to understand and potentially
intervene in neurodevelopmental disorders.

8. The development of the CNS is a
fascinating process that occurs during
embryonic development and continues
into early childhood.
Disruptions or abnormalities during this
process can lead to a wide range of
neurological disorders and
developmental disabilities.
Understanding the mechanisms
underlying CNS development is critical
for advancing our knowledge of brain
development and for developing new
therapies for neurological disorders.

10. A- ECTODERM
DEVELOPMENT

11. sperm Ovum
Fertilization is the fusion between a single sperm & ovum to form a zygote. It could
be considered the actual beginning of intrauterine life.
Zygote

12. Embryonic disc
The embryo well develop into a flattened, unilamellar disc

13. Tri-lamellar- Embryonic disc
Endoderm
Mesoderm
Ectoderm
By Gastrulation, the unilamellar embryonic disc is transformed into a trilaminar
(three-layered) disc formed of three germ layers (ectoderm, mesoderm, endoderm).

14. Cranial side of
Ectoderm
The primitive streak is a critical structure in early vertebrate embryonic
development, specifically during gastrulation with enlarged anterior end (primitive
node – knot- ). The primitive streak appears as a thickened band of cells on the
surface of the ectoderm in the dorsal + caudal half of the embryonic disc.
Primitive streak

15. B- NEURULATION

17. Primitive streak
Notochord
Buried in the mesoderm
The notochord is indeed a fascinating structure found in the embryos of humans. It's
a flexible rod-like structure that provides support during embryonic development.
During early embryonic development, the notochord is formed as ectodermal cells
(primitive node - knot- ) that migrate and buried itself inside the mesoderm.
Cranial side of
Ectoderm

18. Ectoderm
Primitive streak
Notochord
Buried in the mesoderm
Neural plate
The notochord induces the embryonic ectoderm over it to thicken & form the
neural plate. The neural plate is located dorsal to the notochord

19. Ectoderm
Primitive streak
Notochord
Buried in the mesoderm
Neural groove
Neural folds
The neural plate is formed in the middle; after acquiring neural folds, neural plate is
transformed into neural groove.

20. Ectoderm
Primitive streak
Notochord
Buried in the mesoderm
Neural tube
Neural folds begin to fuse together forming the neural tube with anterior and
posterior neuropores.
Anterior neuropore
Posterior neuropore

21. Ectoderm
Neural tube
Neural tube Neural crest cells
The neural tube soon
separates from the surface
ectoderm with neural crest
cells appears dorsal to the
neural tube

23. • Definition:
Neurulation means formation of the neural
tube.
• Timing :
It is started by the 18th day & completed by
the end of the 4th week (28th day).

24. • Stages :
1. Formation of neural plate
2. Formation of neural folds
3. Formation of neural groove
4. Fusion of neural folds
5. Formation of neural tube.
neural folds
neural groove
notochord
Ectoderm
Mesoder
m
endoderm

25. • Development:
ü The notochord induces the embryonic ectoderm over it to thicken & form the
neural plate.
ü The plate is located dorsal to the notochord
Neural plate
neural groove
neural folds
Primitive streak
Fused neural folds
neural tube

26. ü The neural plate invaginates in the middle to form a neural groove which has
neural folds on each side.
ü Neural folds begin to fuse together. The (anterior neuropore) closes on 26th day
Neural plate
neural groove
neural folds
Primitive streak
Fused neural folds
neural tube
Caudal neuropore
Cranial neuropore

27. Neural plate
neural groove
neural folds
Primitive streak
Fused neural folds
neural tube
Cranial neuropore
closed
Fused neural folds
Caudal neuropore
closed

28. ü The neural tube soon separates from the surface ectoderm with neural crest cells
in between
ü The neural tube lies between the surface ectoderm & notochord.
surface ectoderm
neural crest cells
neural tube
notochord

29. ü The cranial part of the tube gives rise to the brain the caudal part gives rise to
spinal cord.
Brain
Spinal cord

30. brain vesicle
Neural tube
Spinal cord
brain hemispheres
Cerebellum
Spinal cord

31. • Neural crest cells are Ectodermal cells related to the neural tube.
• It lies between the neural tube & the overlying surface ectoderm.
Neural crest
cells

32. Neural tube will form [Neurons inside the CNS]:
• Neurons of brain.
• Neurons of spinal cord.
The neural crest will give rise to [Neurons out side the CNS]:
• Neurons of peripheral nervous system (PNS) of nerves, Sheaths of peripheral
nerves (Schwann cells), ganglia, and plexuses
• Cells covering CNS (arachnoid and pia mater of meninges). N.B., (dura mater
from mesoderm).

33. Neural crest cells as well migrate venrally & differentiate into
various cell types in the body:
• Medulla of suprarenal gland
• Melanocytes of the skin epidermis.
• Participate in the development of the face Face
Medulla of suprarenal gland
Melanocytes of epidermis.

34. Treacher Collin’s syndrome
Full facial development does
not occur because the neural
crest cells fail to migrate
properly to the facial region.
Manifested by bilateral
downward slanting eyes,
underdeveloped cheekbones,
and a small jaw
Clinical Insight

35. C- SPINAL CORD
DEVELOPMENT

36. During early embryonic development,
the neural tube forms, which eventually
differentiates into the brain and spinal
cord.
• The caudal (tail) end of the neural
tube elongates to form the spinal cord.
• The cranial (head) end develops into
the brain.
This process is crucial for the formation
of the central nervous system.
Neural tube

37. The neuroepithelium of caudal part of
neural tube gives rise to three layers:
• The inner (ependymal) zone
become the ependymal lining of the
spinal cord central canal.
• The intermediate (mantle) zone
develop into the gray matter of the
spinal cord.
• The outer (marginal) zone
become white matter of the spinal cord.
Inner
(ependymal)
zone
Intermediate
(mantle)
zone
Outer
(marginal)
zone
Ectoderm
Neural crest cells
Neural tube

38. The sulcus limitans is a longitudinal groove on each side of the neural tube dividing
the mantle and marginal zones into a dorsal alar plate and ventral basal plate.
• The alar plate develops into the dorsal horn of gray matter of spinal cord.
• The ventral basal plate develops into the ventral and lateral horns of gray matter
of spinal cord.
Ectoderm
Neural crest cells
Neural tube
dorsal alar plate
sulcus limitans
ventral basal plate
Dorsal horn
Lateral horn
Ventral horn

39. The spinal cord and vertebral column are approximately the same length at the end
of the embryonic period.
The vertebral column grows at a relatively faster rate through the fetal and postnatal
periods of growth.
• At embryo, it fills the whole length of the vertebral canal
• At birth: it ends at the L3
• At adult: ends at the level of L1 & L2 intervertebral disc.
This fast growth of vertebral column will cause the lower thoracic, lumbar and
sacral spinal nerve roots are crowded inferiorly in the vertebral canal (as the cauda
equina, or “horse’s tail”) to reach their appropriate level of exit from the vertebral
column.

40. Relationships in
fetus at 2–3 months
Relationships at
birth
Relationships at
adult
Spinal cord
terminates at
L1
Spinal cord
terminates at
L3
Spinal cord
terminates
near the end
of vertebral
canal
L3
L2
L1
L3
L2
L1
L3
L2
L1

41. Lumbar puncture
A lumbar puncture, also known as a spinal tap, is typically performed between the
third and fourth lumbar vertebrae (L3-L4) or between the fourth and fifth lumbar
vertebrae (L4-L5). This is below the level of the lower end of the spinal cord, which
typically ends at the level of the first or second lumbar vertebra (L1-L2) in adults.
Clinical Insight

42. Uses
• Diagnostic uses:
Obtaining C.S.F sample for analysis.
• Therapeutic uses:
Injection of local anesthetics and antibiotics.
C.S.F withdrawal to decrease intra-cranial pressure.
Clinical Insight

43. Spina Bifida
A birth defect in the baby that occurs when the bony vertebral column and the spinal
cord do not develop completely. It could be either occulta or cystica.
Clinical Insight

44. 1- Spina bifida occulta
• It is a defect in the vertebral column
• Covered by skin
• Usually does not involve underlying neural tissue.
• Occurs in L5 or S1.
• Only evidence a small dimple .
• Produces no clinical symptoms
Clinical Insight

45. Small dimple
Clinical Insight

46. 2- Spina bifida cystica
• The baby has cyst like sac.
• Meningo-cele: Sac contains [meninges and CSF]
• Myelo-meningo-ocele: Sac contains [meninges, CSF] + [spinal cord, nerve
roots]
Clinical Insight

47. D- CEREBRUM,
CEREBELLUM, BRAIN STEM
DEVELOPMENT

48. Near end of the 1st month, brain
begins to develop from cranial
part of neural tube.
Flexures and swellings
distinguish:
• forebrain (prosencephalon)
• midbrain (mesencephalon)
• hindbrain (rhombencephalon)
Large optic vesicles extend from
the forebrain, will develop into
the optic nerves and retina of the
eyes.
Cranial
part
of
neural
tube
Caudal
part
of
neural
tube
forebrain (prosencephalon)
midbrain (mesencephalon)
hindbrain (rhombencephalon).
Spinal cord

49. DEVELOPMENT OF
FOREBRAIN
By 5 weeks the forebrain
(prosencephalon) has two
subdivisions
• Telencephalon
• Diencephalon
Cranial
part
of
neural
tube
Caudal
part
of
neural
tube
hindbrain (rhombencephalon)
midbrain (mesencephalon)
forebrain (prosencephalon)
Spinal cord
• Telencephalon
• Diencephalon

50. DEVELOPMENT OF
MIDBRAIN
By 5 weeks the midbrain
(mesencephalon) has no
significant subdivisions
Cranial
part
of
neural
tube
Caudal
part
of
neural
tube
hindbrain (rhombencephalon)
midbrain (mesencephalon)
forebrain (prosencephalon)
Spinal cord

51. DEVELOPMENT OF
HIND BRAIN
By 5 weeks the hindbrain
(rhombencephalon has two
parts
• Metencephalon
• Myelencephalon.
Cranial
part
of
neural
tube
Caudal
part
of
neural
tube
hindbrain (rhombencephalon)
midbrain (mesencephalon)
forebrain (prosencephalon)
Spinal cord
• Myelencephalon
• Metencephalon

52. By 3 months the major regions, structures, and features of the brain are
recognizable.
• The telencephalon differentiate into [cerebral hemispheres, lentiform nucleus
and caudate nucleus].
Telencephalon cerebral hemispheres

53. By 3 months the major regions, structures, and features of the brain are
recognizable.
• The diencephalon differentiate into thalamus, hypothalamus, epithalamus, and
subthalamus.
Diencephalon thalamus

54. By 3 months the major regions, structures, and features of the brain are
recognizable.
• The mesencephalon differentiate into midbrain.
mesencephalon midbrain

55. By 3 months the major regions, structures, and features of the brain are
recognizable.
• The metencephalon differentiate into cerebellum and pons
metencephalon
Cerebellum
pons
pons
Cerebellum

56. By 3 months the major regions, structures, and features of the brain are
recognizable.
• The myelencephalon is now the medulla oblongata.
myelencephalon medulla oblongata

57. The development of cerebral hemispheres changes dramatically from 3 months of
the intrauterine life to birth with the rapid enlargement of the cerebral hemispheres
and the elaboration of their frontal, parietal, temporal, and occipital lobes.
The surface of the hemispheres becomes convoluted sulci separating a number of
irregular, folded gyri. This greatly increases the surface area of the cerebral cortex.

59. The growth of the human
brain does continue beyond
birth and into childhood and
adolescence. At old age, there
is a decline in the number of
neurons due to apoptosis

60. Anencephaly
Serious birth defect in which a baby
is born without parts of the brain and
skull. This condition typically occurs
during early development when the
neural tube fails to close completely,
resulting in the absence of a major
portion of the brain, skull, and scalp.
Babies born with anencephaly are
usually unable to survive for more
than a few hours or days after birth.
It's a heartbreaking condition that can
have profound emotional effects on
families.
Clinical Insight

61. The cavity of the neural tube enlarges to form:
• Lateral ventricles
• 3rd ventricle
• Cerebral aqueduct
• 4th ventricle
Lateral ventricle
3rd ventricle
Cerebral aqueduct
4th ventricle
Cavity of neural tube

62. Formative Quiz

63. Q1 A newborn baby is brought to the pediatrician due to difficulty moving the lower
limbs. Physical examination reveals absent reflexes in the legs and flaccid paralysis
below the waist. MRI shows a small, fluid-filled sac protruding from the lower
back.
Which of the following conditions is most likely present in this patient?
A) Arnold-Chiari malformation
B) Spina bifida occulta
C) Anencephaly
D) Myelomeningocele
E) Dandy-Walker syndrome

64. Q2 A 3-month-old infant presents with failure to thrive and developmental delays.
On examination, the infant has a small head circumference, wide fontanelles, and
poor muscle tone. MRI shows an absence of the cerebral hemispheres, with
rudimentary brain tissue replaced by cerebrospinal fluid.
Which of the following conditions is the most likely diagnosis?
A) Holoprosencephaly
B) Microcephaly
C) Encephalocele
D) Anencephaly
E) Dandy-Walker syndrome

65. Q3 A 26-year-old female presents to her primary care physician for a routine check-
up. During the physical examination, the physician notices a tuft of hair over the
lower lumbar region. Further examination reveals no other abnormalities.
What is the most likely diagnosis?
A) Spina bifida occulta
B) Spina bifida cystica
C) Meningomyelocele
D) Myelomeningocele
E) Sacral agenesis

66. Q4 A 34-year-old male presents with lower back pain and occasional leg weakness.
MRI of the lumbar spine reveals a bony defect in the posterior elements of the
lumbar vertebrae with no herniation of spinal cord or meninges. What is the most
likely diagnosis?
A) Spina bifida cystica
B) Meningomyelocele
C) Spina bifida occulta
D) Myelomeningocele
E) Sacral agenesis

67. Q5 A 50-year-old male is admitted to the hospital with symptoms suggestive of
Guillain-Barré syndrome. The physician decides to perform a lumbar puncture to
confirm the diagnosis.
Which of the following landmarks should guide the physician in identifying the
appropriate lumbar vertebral level for the procedure?
A) Inferior angle of the scapula
B) Iliac crest
C) Superior border of the iliac crests
D) 12th rib
E) Anterior superior iliac spine

68. Q1 Myelomeningocele
Q2 Anencephaly
Q3 Spina bifida occulta
Q4 Spina bifida occulta
Q5 Superior border of the iliac crests

69. List of Texts and Recommended Readings
• Last's Anatomy, Regional and Applied. Chummy S. Sinnatamby. 12th edition 2011, ISBN:13 - 978 0 7020
3394 0 (Available in ClinicalKey: https://www.clinicalkey.com/#!/browse/book/3-s2.0- C2009060533X)
• Estomih Mtui, Gregory Gruener and Peter Dockery. Fitzgerald's Clinical Neuroanatomy and
Neuroscience. 7th edition; 2016, ISBN: 13 - 978-0-7020- 6727-3 (Available in ClinicalKey:
https://www.clinicalkey.com/#!/browse/book/3-s2.0- C20130134113
• Drake, Richard L. Gray's Anatomy for Students, Third Edition, Elsevier Saunders 2015. ISBN-13: 978-
0702051319 (Available in ClinicalKey: https://www.clinicalkey.com/#!/browse/book/3- s2.0-
C20110061707).
• Sobotta Atlas of Human Anatomy. F. Paulsen. Vol.1, 15th Edition; 2013, ISBN: 9780702052514 (Available in
ClinicalKey: https://www.clinicalkey.com/#!/content/book/3- s2.0-B9780702052514500067)
• Sobotta Atlas of Human Anatomy. F. Paulsen. Vol.2, 15th Edition; 2013, ISBN:13 - 978-0-7020-5252-1

70. https://www.slideshare.net/ahmedsahm
edtanta
USMLE FULL SOURCES

71. Recap