development of nervous system

1. DEVELOPMENT OF NERVOUS
SYSTEM
Presenter: Dr Ira K.C.
Moderator: Dr Anish Joshi

4. • At the end of week two, a structure called the primitive streak appears as a groove in the epiblast
layer of the bilaminar disk.
• Cells within the epiblast migrate downward through the primitive streak, giving rise to three
layers from the initial two. These three germinal layers form the trilaminar embryonic disk:
• Ectoderm: outside, surrounds other layers later in development, generates skin and nervous
tissue.
• Mesoderm: middle layer, generates most of the muscle, blood and connective tissues of the
body and placenta.
• Endoderm: eventually most interior of embryo, generates the epithelial lining and associated
glands of the gut, lung, and urogenital tracts The nervous system is derived from the ectoderm,
which is the outermost layer of the embryonic disc.
GASTRULATION

6. NEURULATION
• In the third week of development, the notochord appears in the
mesoderm. The notochord secretes growth factors which stimulate the differentiation of
the overlying ectoderm into neuroectoderm – forming a thickened structure known as the
neural plate.
• The lateral edges of the neural plate then rise to form neural folds. The neural folds move
towards each other and meet in the midline, fusing to form the neural tube (precursor to the
brain and spinal cord)
• During fusion of the neural folds, some cells within the folds migrate to form a distinct cell
population – known as the neural crest. They give rise to a diverse cell lineage –
including melanocytes, craniofacial cartilage and bone, smooth
muscle, peripheral and enteric neurons and glia

9. • Folding and closure of the neural tube occurs first in the
cervical region
• The neural tube then “zips” up toward the head and toward
the tail, leaving two openings which are the anterior and
posterior neuropores
• The anterior neuropore closes around day 25.
• The posterior neuropore closes around day 28.

10. NEURAL TUBE DEFECTS
1. Anencephaly:
• Characterised by the failure of cephalic part of neural tube closure
• As a result, vault of the skull does not form, leaving the malformed
brain exposed
• Later this tissue degenerates, leaving necrotic tissue
• Brainstem is intact
• In some cases, the closure defect extends caudally into the spinal
cord and the abnormality is known as Craniorachischisis
• Swallowing reflex is absent so last 2 months of pregnancy is
characterised by polyhydramnios

11. 2. Spina Bifida
Spina Bifida occulta
• Due to lack of fusion of vertebral arches
• covered by skin and does not involve the underlying neural tissue
• Occurs in the sacral region (S1-S2)
• Marked by patch of hair overlying the affected region
Spina Bifida Aperta
1. Meningocele
• Meninges with CSF herniate through a defect in the posterior vertebral
arches
• Presents as a fluctuant midline mass that transilluminate, usually in the
lower back
• Covered with skin
2. Meningomyelocele
• Most severe form
• Meninges with CSF and functional neural tissues like nerves and
spinal cord protrude through the defect

12. DERIVATIVES OF NEURAL CREST CELLS
1. Peripheral Nervous System
• Dorsal root ganglia
• Parasympathetic ganglia
• Sympathetic ganglia
2. Supporting cells
• Schwann cells
• Neuroglial cells of peripheral ganglia
3. Leptomeninges
4. Adrenal Medulla
5. Parafollicular cells of thyroid
6. Melanocytes
7. Cranial Vault

13. 4 weeks 5 weeks

14. TELENCEPHALON
• Generates cerebral cortex:
– Neocortex: 6-layered cortex of frontal, temporal,
parietal, and occipital lobes
– Archicortex: 3-layered cortex of hippocampus and
dentate gyrus
– Paleocortex: olfactory cortex
• Generates basal ganglia:
– Caudate nucleus, lentiform nucleus, putamen,
amygdala
• Commissures interconnect the cerebral hemispheres:
– Anterior commissure: interconnects olfactory
structure and some of temporal lobes
– Hippocampal commissure: interconnects the
hippocampi
– Corpus callosum: interconnects neocortex

15. HOLOPROSENCEPHALY
• Due to defective formation of prosencephalon and inadequate induction
of forebrain structures
• 3 types: alobar, semilobar and lobar
• Alobar: single ventricle, absent falx and nonseparated deep cerebral
nuclei
Features:
• Single nostrils
• Choanal atresia
• Solitary single incisor tooth
• Cyclopia
• Synophthalmia
• Cebocephaly

16. DIENCEPHALON
• Pineal gland: sleep-wake cycle, secretes melatonin
• Epithalamus: masticatory and swallowing functions
• Thalamus: major relay of sensory input to cerebral
cortex
• Hypothalamus: master regulatory center (autonomic
and endocrine) and also limbic system (emotion &
behavior)
• Hypophysis/infundibulum: posterior pituitary gland,
secretes ADH and oxytocin
• Optic cup: retina of eye

17. MESENCEPHALON
• Alar plate generates superior and inferior colliculi
• Inferior colliculus: auditory relay
• Superior colliculus: visual relay
• Basal plate generates 4 motor tracts:
• Somatic efferent (motor output to extraocular muscles, CN III,
IV)
• Visceral efferent (motor output to ciliary ganglion of the eye,
CN III)
• Red nucleus (motor relay to flexor muscles of the upper limb)
• Substantia nigra (dopaminergic output to the basal ganglia of the
telencephalon)

18. METENCEPHALON
• Rhombic lip develops into cerebellum
• Alar plate develops into 4 sensory tracts:
• Pontine nuclei (cerebellar input)
• Somatic afferent (general sensation from the face, tongue,
and extraocular muscles, CN V, VI, VII)
• Special visceral afferent (taste, CN VII)
• General visceral afferent (autonomic input from soft palate
& pharynx, CN VII)
• Basal plate develops into 3 motor tracts:
• General visceral efferent (autonomic output to salivary and
lacrimal glands, CN VII)
• Special visceral efferent (innervation of muscles of the face,
via CN VII, and of mastication, via CN V)
• Somatic efferent (innervation of lateral rectus muscle of the
eye, via CN VI)

19. MYELENCEPHALON
• Alar plate develops into 4 sensory tracts:
• Olivary nucleus (cerebellar input)
• Somatic afferent (general sensation from the face, via CN V, external ear, auditory meatus, and
eardrum via CN IX, X)
• General visceral afferent (autonomic input, CN IX, X)
• Special visceral afferent (taste, CN IX, X)
• Basal plate develops into 3 motor tracts:
• General visceral efferent (autonomic output, CN IX, X)
• Special visceral efferent (innervation of pharyngeal arch muscles of the larynx & pharynx, CN IX,
X, XI)
• Somatic efferent (innervation of skeletal muscles of the tongue, CN XII)

20. VENTRICLES
• Derived from central canal of the neural tube
• As regions of the brain take shape, the ventricles are
shaped into dilated regions (e.g. lateral ventricle, 3rd
ventricle, 4th ventricle) connected by channels (e.g.
foramen of Monro, cerebral aqueduct)
• Septum pellucidum separates the lateral ventricles
• Ependymal cells in the roof of the lateral, 3rd, and 4th
ventricle become specialized for the production of
CSF
• Blockage of the communicating channels can cause
dilation of the ventricles or hydrocephalus

21. HYDROCEPHALUS
• Results from increased production, impaired circulation or absorption
of CSF
• Obstructive/ Non-communicating: due to aqueductal stenosis or
lesions in the fourth ventricles
• Communicating: due to obliteration of the subarachnoid cisterns or
malfunction of the arachnoid villi
Features:
• Infant: accelerated rate of enlargement of head, wide and bulging
anterior fontanelle, sunset sign
• Older children: headache, irritability, lethargy, poor appetite

22. CHIARI MALFORMATION
Type 1:
• Cerebellar tonsil descends down the foramen magnum
• Obstruction of the caudal portion of the fourth ventricle
• Not associated with hydrocephalus
• Features: recurrent headache, neck pain, urinary frequency,
progressive lower extremity spasticity
Type II:
• Failure of pontine flexure development, with elongation of fourth
ventricle and kinking of brainstem
• Displacement of inferior vermis, pons, medulla into cervical canal
• Progressive hydrocephalus with myelomeningocele
• Features: stridor, weak cry, apnea

23. DANDY WALKER MALFORMATION
• Developmental failure of the roof of the fourth ventricle
Characterised by:
• Agenesis or hypoplasia of cerebellar vermis
• Cystic dilatation of fourth ventricle
• Enlargement of posterior cranial fossa
Features:
• Cerebellar ataxia
• Delayed motor and cognitive milestones
• Rapid increase in head size and prominent occiput

24. SPINAL CORD
• Develops from the caudal part of neural tube
• By middle of 5 weeks, the transverse section of
spinal cord will form 3 layers:
Matrix (ependymal) zone: thick and lines the
enclosed cavity (neurocele).
Its numerous cells undergoing mitosis produce
neuroblasts and spongioblasts;
the former develop into neurons and the latter into
neuroglial cells.
Mantle zone: forms grey matter
Marginal zone: forms white matter

25. WEEKLY IRON–FOLIC ACID SUPPLEMENTS CONTAINING 2.8 MG FOLIC ACID
ARE ASSOCIATED WITH A LOWER RISK OF NEURAL TUBE DEFECTS THAN
THE CURRENT PRACTICE OF 0.4 MG: A RANDOMISED CONTROLLED TRIAL
IN MALAYSIA
K A I T LY N L I S A M S O N 1 , S U P E N G L O H 3 , S I E W S I E W L E E 3 , D I A N C S U L I S T Y O N I N G R U M 4 , 5 , G E O K L I N
K H O R 3 , Z A L I L A H B I N T I M O H D S H A R I F F 3 , I R M I Z A R I N A I S M A I 3 , L I S A N Y E L L A N D 4 , 6 , S H A L E M
L E E M A Q Z 4 , M A R I A M A K R I D E S 4 , 5 ,
Abstract
• Introduction Weekly iron–folic acid (IFA) supplements are recommended for all menstruating women in countries where
anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in
question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most
weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose
effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack
of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared
with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk.
• Methods We conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were
randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks.
• Results At 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those
receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving
2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in
the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate
>748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group.
• Conclusion Weekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg.
Increased availability and access to the 2.8 mg formulation is needed.

26. BIBLIOGRAPHY
• Langman’s Medical Embryology, 12th edition
• Snell’s Clinical Neuroanatomy, 10th edition
• Nelson Textbook of Pediatrics, 21st edition

27. THANKYOU