saRavanan

EMBRYOLOGY OF

BRAIN

What’s on your mind?

The human brain is the most complex mass of protoplasm on

earth-perhaps even in our galaxy.

-Marian C. Diamond and Arnold B. Scheibel

FORMATION OF NEURAL TUBE

Formation of the neural groove, neural tube and neural crest

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.

PRIMARY BRAIN VESICLES & THEIR SUB DIVISIONS

FLEXURES OF NEURAL TUBE

DEVELOPMENT OF EXTERNAL FORM OF BRAIN

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

DEVELOPMENT OF VENTRICLES OF BRAIN

LAYERS OF NEURAL TUBE

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

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

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

• 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.

Metencephalon

Transverse section through the caudal part of metencephalon

CEREBELLUM

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

• 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.

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

• 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-

• 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

• 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

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

MESENCEPHALON

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.

Diencephalon

Roof Plate and Epiphysis

Alar Plate, Thalamus, and Hypothalamus

DEVELOPMENT OF THALAMUS &HYPOTHALAMUS

Hypophysis or Pituitary Gland

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.

Telencephalon

Cerebral Hemispheres

CEREBRAL HEMISPHERE&LATERAL VENTRICLE

• Development of gyri and sulci on the lateral surface of the cerebral hemisphere.

• A. 7 months. B. 9 months.

FORMATION OF CHOROID FISSURE

FORMATION OF TELA CHOROIDEA &CHOROID PLEXUS

Cortex Development• The cerebral cortex develops from the pallium

which has two regions: – (a) the paleopallium, or archipallium– (b) the neopallium

Commissures

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

• 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

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

• 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

MOLECULAR REGULATION OF BRAIN DEVELOPMENT

“Biology gives you a brain. Life turns it into a mind.” 

― Jeffrey Eugenides, Middlesex