CNS Embryo

• Neurulation

  1. Neural plate formation

  2. Neural folds formation

  3. Neural tube formation

  4. Neuropore closure

  
• Neural tube

  • The primordium of the brain and spinal cord which forms during neurulation

  
• Development of the ependymal, mantle and marginal layers

  Germinal cells proliferate (simple columnar epithelium) until the neural tube becomes pseudostratified.

  • Inner ependymal layer forms: simple columnar epithelium; lines central canal of the spinal cord
  • Middle mantle layer forms: grey matter; two cells - neuroblasts (forms neurons) & glioblasts (forms astrocytes & oligodendrocytes)
  • Outer marginal layer forms: white matter; axons of neurons & mesenchyme which forms meninges.
• Development of the alar and basal plates of the primitive spinal cord

  Four bulges form as a result of the proliferation of the mantle layer:

  • Two dorsal bulges (alar plates) and two ventral bulges (basal plates)
  • The dorsal bulges/alar plates consist of sensory neurons; form dorsal horn of spinal cord.
  • The ventral bulges/basal plates consist of motor neurons; form ventral horn
  • As the alar and basal plates form, a cleft called the sulcus limitans will form on either side of the lumen of the spinal cord.
• Sulcus limitans

  Cleft that divides the spinal cord into sensory and motor parts

  
• "Retraction" of the spinal cord

  ⇒By the end of W8, the trunk elongates and the newly formed spinal cord does not keep up with the pace of the trunk, gets left behind and, appears to retract.

  ⇒By the end of term, the end of the spinal cord = level of L3. In adult life, it terminates at IV disc between L1 and L2. (end of spinal cord = conus medullaris)

  ⇒Due to the discrepancy in growth between the vertebral column and spinal cord, the nerve roots will lie in a vertical direction within the vertebral canal forming the cauda equina
• Types of spina bifida

  • Spina bifida is not really an abnormality of the spinal cord but rather of the vertebral column.
  • Two main types: Spina bifida occulta & Spina bifida cystica/meningocele
  • Other: Spina bifida with meningomyelocoele & Spina bifida with myeloschisis
• Primary brain vesicles

  • Prosencephalon (forebrain)
  • Mesencephalon (midbrain)
  • Rhombencephalon (hindbrain)
  • In order from cranial to caudal; forms at week 5
• Secondary brain vesicles

  • Prosencephalon (forebrain) -> cranial Telencephalon & caudal Diencephalon
  • Mesencephalon (midbrain) does not divide
  • Rhombencephalon (hindbrain) -> cranial Metencephalon & caudal Myelencephalon
  • *Forms at week seven of development
• Organs formed from secondary brain vesicles

  1. The telencephalon forms the cerebrum.

  2. The diencephalon forms the thalamus, hypothalamus and epithalamus

  3. The mesencephalon is the midbrain

  4. The metencephalon forms the cerebellum and pons

  5. The myelencephalon forms the medulla oblongata
• Brain flexures

  • Cephalic flexure: between midbrain and forebrain (at region of mesencephalon), where telencephalon bents ventrally; during 3rd week
  • Cervical flexure: between myelencephalon and the spinal cord, caudal to the metencephalon; during 5th week
  • Pontine flexure: between metencephalon and myelencephalon of the rhombencephalon; in the opposite direction to the other two flexures; during 7th week
• Development of the telencephalon

  1. Telencephalic vesicles form the cerebral hemispheres. The cavities within the telencephalic vesicles form the lateral ventricles

  2. Telencephalon medium forms; it is the non-distended part of the telencephalon. The two cavities within the telencephalon median and diencephalon coalesce to form the 3rd ventricle

  3. The lamina terminalis marks the closure of the anterior neuropore and induces the formation of the cranial vault in the skull
• Describe the formation of the pallium and Colliculus ganglionaris from the telencephalic vesicles

  • The cranial part of the telencephalic vesicles becomes thin, forming the pallium (p). 
  • The floor, or caudal part dilates to form the Colliculus ganglionaris (cgang)
• Internal capsule

  Divides colliculus ganglionaris, forms striate body
• Development of primitive cortex

  1. Cells migrate from mantle layer to marginal layer of pallium to form a single layer of grey matter

  2. Cortex forms six layers
• Mesencephalon

  • Connects diencephalon to metencephalon and myelencephalon
  • Accommodates fibres, narrows to form cerebral aqueduct (which connects the 3rd & 4th ventricles)
• Fourth ventricle

  Formed by cavities in metencephalon and myelencephalon
• Derivatives of brain cavities

  • Lateral ventricles from telencephalic vesicles
  • Third ventricle from telencephalon medium and diencephalon
  • Cerebral aqueduct from mesencephalon
  • Fourth ventricle from metencephalon and myelencephalon
• Congenital brain malformations

  • Microcephaly: Underdeveloped/small brain, associated with small cranium
  • Anencephaly: Absence of brain, due to failure of anterior neural pole to close
  • Hydrocephalus: Excessive CSF accumulation due to drainage blockage, leads to enlarged brain and skull
• Neural Plate formation

  At the beginning of the third week of intra-uterine life, the notochord induces the overlying ectoderm to proliferate and thicken to form the neural plate.

  • This strip of columnar ectodermal cells is known as the neural plate
  • At the edges of the plate, the columnar cells meet the flattened cells of surface ectoderm.
• Neural fold formation

  The rapidly dividing cells of the neural plate become heaped at this junction to form neural folds and this results in the formation of the neural groove between the folds, at the midline of the neural plate.
• Neural tube formation

  As the folds enlarge, the groove deepens/invaginates further and the folds, bending towards one another, meet and fuse in the middle of the neural plate.

  • The rest of the ectoderm is pinched off
  • The anterior and posterior neuropores remain open temporarily.
  • While the neural folds are developing, a special group of cells detach and differentiate in the folds of the crests These cells are known as neural crest cells.
• Neuropore closure

  By the end of the fourth week of development, the neural folds have fused completely, the neuropores have closed, and the surface ectoderm has separated from the neural tube.

  • The notochord only induces the overlying ectoderm. The rest of the ectoderm will become surface ectoderm, forming the epidermis of the skin
• What are cranial & caudal neuropores?

  Following the process of neurulation, the neural tube remains open at the caudal and cranial ends.

  • These openings are the caudal and cranial neuropores, aka posterior and anterior neuropores.
  • These neuropores must close before the CNS can form, so that the CNS is a closed system.
• Describe each type of spina bifida

  A = Spina bifida occulta

  ⇒No structures protrude through this defect and it is characterised by a tuft of hair and a dimple around L5 or S1

  
  

  B = Spina bifida cystica/meningocele

  ⇒The cerebrospinal fluid and meninges protrude through the defect to form a cyst posteriorly
• Describe each type of spina bifida

  C = Spina bifida with meningomyelocoele

  ⇒The cyst consists of three things: CSF, the spinal cord and meninges (myelo=spinal cord)

  
  

  D = Spina bifida with myeloschisis.

  ⇒This is an open spinal cord; the neural tube did not close (i.e the two neural folds did no
• Structure of vertebrae

  • Cervical vertebra
  • Primary and secondary curves
  • Vertebral column curves
• Embryonic development of the vertebral column

  1. Develops during the 4th week of intra-uterine life from the sclerotome of somites

  2. Cranial part - less condensed

  3. Caudal part - more condensed

  4. Formation of intervertebral disc

  5. Development of neural arches, transverse processes, costal processes
• Paraxial mesoderm

  • Somite differentiation
  • Migration of sclerotome cells
• The vertebral column develops from the sclerotome of somites
• The notochord, centrum, neural arches, transverse and costal processes develop during vertebral column development
• Fate of costal process

  • In cervical region it forms anterior and lateral boundary of transverse foramen
  • In thoracic region it elongates to form ribs
  • In lumbar region it fuses with transverse process to form anterior part
  • In upper sacral region it forms anterior portion of ala of sacrum
• Chondrification

  1. Formation of primary ossification centres

  2. Formation of secondary ossification centres
• Three primary ossification centres form during the 8th week of development: one in the centrum, two in each neural arch
• Five secondary ossification centres form after puberty: superior and inferior rims of vertebral body, tip of spinous process, tip of each transverse process
• Congenital abnormalities of the vertebral column


  • Lumbarization and sacralization
  • Klippel-Feil syndrome
  • Hemivertebra
  • Spina bifida occulta
  • Spina bifida with meningocoele
  • Spina bifida with meningomyelocoele
  • Spina bifida with myeloschisis
• Klippel-Feil syndrome is characterized by shortness of the neck, low hairline, and restricted neck movements, often with fewer than normal cervical vertebral bodies
• Hemivertebra is a basis for scoliosis
• Spina bifida occulta involves incomplete closure of the vertebral arch without a protruding spinal cord or meninges
• Spina bifida with meningomyelocoele involves protrusion of both the meninges and spinal cord through the vertebral arch defect