The human brain is the most complex organ on Earth. It develops from the neural tube which forms the basic structure of the central nervous system. As the brain develops from early embryonic stages through fetal development, different regions form including the rhombencephalon (medulla and pons), mesencephalon, and prosencephalon (telencephalon and diencephalon). Precisely regulated molecular processes guide the formation, migration and differentiation of neurons and glial cells in each brain region. Malformations can occur if these processes are disrupted, leading to neurological disorders.

1. saRavanan

2. The human brain is the most complex
mass of protoplasm on earth-perhaps
What’s on your mind?
even in our galaxy.
-Marian C. Diamond and Arnold B. Scheibel

5. FORMATION OF NEURAL TUBE

6. Formation of the neural groove, neural tube and neural crest

7. A. Dorsal view of human embryo (approx. day 22) B. (approx. day 23)
C. SEM of mouse embryo at stage similar to that of A.

11. Lateral views of the fetal brain, from 10 to 40
weeks of gestational age.

15. RHOMBENCEPHALON
• Consists of the myelencephalon, the most
caudal of the brain vesicles, and the
metencephalon, which extends from the
pontine flexure to the rhombencephalic
isthmus

16. Myelencephalon
• Gives rise to medulla oblongata
• Differs from spinal cord: its lateral walls are everted
A. Dorsal view of the floor of the 4th ventricle in a 6-week embryo
B-C. Myelencephalon at different stages of development

17. Lateral view of the brain vesicles in an 8-week embryo

18. Metencephalon
• The metencephalon, similar to the
myelencephalon, is characterized by basal and
alar plates.
• Two new components form:
– (a) the cerebellum, a coordination center for
posture and movement,
– (b) the pons, the pathway for nerve fibers
between the spinal cord and the cerebral and
cerebellar cortices.

19. Transverse section through the caudal part of
metencephalon

20. CEREBELLUM

23. A. 8 weeks (approx. 30 mm) B. 12 weeks (70 mm)
C. 13 weeks D. 15 weeks.

24. • In the sixth month of development, the external
granular layer gives rise to various cell types.
• These cells migrate toward the differentiating
Purkinje cells and give rise to granule cells.
• Basket and stellate cells are produced by
proliferating cells in the cerebellar white matter.

26. CEREBELLAR MALFORMATIONS
AND MALFUNCTIONS
• Hypoplasias- under development
• Dysplasias- abnormal tissue development
• Heterotopias- misplaced cells
• Schizophrenia- related to early defects in
neuronal migration, the expression of
neurotransmitter receptors, or myelination
• Ataxia- disruption of coordination; result from
degeneration of cerebellum

27. • Trisomy 13- vermis is hypoplastic and neurons
are heterotopically located in the white matter
• Cerebellar dysplasia- usually of the vermis;
characteristic of Trisomy 18
• Trisomy 21 (Down Syndrome)- may involve
abnormalities of the Purkinje and granule cell
layers
• Chromosome deletion syndromes:
– 5p-(cri du chat), 13q-, 4p-

28. • Friedriech ataxia- autosomal recessive; affects
the dorsal root ganglia, spinal cord, cerebellum;
progressive disorder
• Other autosomal recessive cerebellar ataxia
syndromes: Ataxia- telanglectasia, Marinesco-
Sjogren syndrome, Gillespie syndrome, Joubert
syndrome, congenital disorders of glycosylation
• Olivopontocerebellar atophy- caused by
deficiency in the excitatory neurotransmitter
glutamate, resulting from deficiency in
glutamate hydrogenase

29. • Cerebrospinal ataxia syndromes:
– Many are caused by unstable CAG trinucleotide
repeat tracts within the coding region of genes
– CAG codes for glutamine; polyglutamine disorders
occur when tract of glutamine residues reaches
the disease-causing threshold.
– Genetic anticipation can cause the worsening of
the disease in successive generations

30. PONS Pons is formed by proliferation of
cell and fiber tracts on ventral side
of metencephalon

31. MESENCEPHALON

33. proSENCEPHALON
• The prosencephalon consists of the:
– telencephalon, which forms the cerebral
hemispheres, and the
– diencephalon, which forms the optic cup
and stalk, pituitary, thalamus,
hypothalamus, and epiphysis.

34. Diencephalon

35. Roof Plate and Epiphysis

37. Alar Plate, Thalamus, and Hypothalamus

40. Hypophysis or Pituitary Gland

41. Hypophyseal Defects
• Occasionally a small portion of Rathke’s pouch
persists in the roof of the pharynx as a pharyngeal
hypophysis.
• Craniopharyngiomas arise from remnants of
Rathke’s pouch.

42. Telencephalon

43. Cerebral Hemispheres

46. • Development of gyri and sulci on the lateral
surface of the cerebral hemisphere.
• A. 7 months. B. 9 months.

50. Cortex Development
• The cerebral cortex develops from the pallium
which has two regions:
– (a) the paleopallium, or archipallium
– (b) the neopallium

52. Commissures

54. Congenital Malformations of
Cerebral Cortex
• Classical lissencephaly (incidence: 1/100,000 live births)
– Results from incomplete neuronal migration to the
cerebral cortex during the 3rd and 4th months of gestation
– Pachygyria (broad, thick gyri), Agyria (lack of gyri),
heterotopia (cells in aberrant positions), enlarged
ventricles, corpus callosum malformations
– Newborns appear normal but sometimes have apnea,
poor feeding, or abnormal muscle tone
– Patients later develop seizures, profound mental
retardation, mild spastic quadriplegia

55. • Subcortical Band Heterotopia
– Believed to result from aberrant migration
of differentiating neuroepithelial cells
– Patients have bilateral circumferential and symmetric
ribbons of gray matter located just beneath the
cortex and separated from it by thin band of white
matter -> double cortex syndrome
– Seizures, mild mental retardation, behavioral
anomalies often present in infancy
– Intelligence can be normal and seizures may begin
later in life
– X-linked lissencephaly and SBH

56. Genes related to lissencephaly and SBH
• LIS1- encodes a protein that functions as a
regulatory subunit of platelet activating factor
acetylhydrolase, which degrades platelet
activating factor and involved in microtubule
dynamics
• Doublecortin- highly expressed in fetal
neurons and their precursors during cortical
development; protein associated with
microtubules

57. • Kallman syndrome
– characterized by anosmia (loss of sense of smell) or
hyposmia (diminished sense of smell) and
hypogonadism.
– X-linked form caused by KAL1, which encodes an
extracellular matrix glycoprotein called ANOSMIN-1

58. MOLECULAR REGULATION OF
BRAIN DEVELOPMENT

62. “Biology gives you a brain.
Life turns it into a mind.”
― Jeffrey Eugenides, Middlesex