Histogenesis of cerebral cortex and cerebellar cortex, NIT.pptx

Histogenesis of cerebral
cortex and cerebellar cortex,
Molecular mechanisms of
neuronal migration
Nitish kumar
M.Sc Neurotechnology
20/02/2023

Contents
• Breif Intoduction to histology of cerebral and
cerebellar cortex.
• Histogenesis of cerebral cortex
• Histogenesis of cerebellar cortex.
• Molecular mechanism of neuronal migration.

Development of cerebrum
• The prosencephalon divides into telencephalon and
diencephalon which consists of 2 lateral outpouchings as
cerebral hemisphere.
• The cavity of prosencephalon forms lateral ventricles
(right and left) that communicates with 3rd ventricle
through interventricular foramen.
• The development can be studies on the basis of
development during first 2 months and after 2nd month.

Development during first 2 months
• Each cerebral hemisphere
consists of two parts:
A.Thin superior pallium
B. Thick basal part
• Cells from basal part
migrate into the pallium
that
forms cerebral cortex.
• Remaining cells of basal
part forms corpus
striatum.

• The junctional zone of two pallium (cerebral cortex)
is very thin and gets invaginated by choroid plexus.
• Pallium grows and gets differentiated into allocortex
and neopallium/cortex. Human brain consists of 90%
of
neopallium.
• Allocortex = archipallium + paleopallium.
• Efferent and afferent fibres from the cerebral cortex
form internal capsule.

Development after 2nd month
• Neopallium overgrows and compresses the
allocortex.
• Increase in the cortical mass reduces ventricular
cavity.
• In the floor of cerebral hemisphere, group of
neurons condenses to form striated nuclei.
• These striated nuclei get transversed by fibres
(axons) of internal and external capsule.

• Striated nuclei differentiate into three groups:-
1. Lateral neostriatal nuclei: They form caudate
nucleus, putamen and claustrum.
2. Medial paleostriatal nuclei: They form globus
pallidum.
3. Archeostriatal nuclei: They form amygdaloid
nucleus below the lenticular nucleus. Soon, the
putamen and globus pallidum fuse to form lentiform
nucleus.

Development of the lobes
• Cerebral cortex grows in various directions to
form
• various lobes in the following manner:
– Ventral growth forms frontal lobe.
– Dorsal growth forms occipital lobe.
– Parietal (lateral) growth forms parietal lobe.
– Occipital pole expands ventrally to form
temporal lobe.

Effects of growing cerebral
hemishpheres
• Growth of occipital and temporal lobe results in
formation of inferior horn and posterior horn of
lateral ventricles.
• Caudate nucleus turns around the ventricle and
becomes C shaped.
• Sulci and gyri starts forming due to continued
growth of cerebral cortex.
• A part of cortex covering the external surface of
corpus striatum grows relatively slower. This part
forms insula.
• From the frontal lobe, elongated evagination
develops to form olfactory bulb.

Commissures of telencephalon
• Thickened band of fibres develops in lamina
terminalis as follows:
1. Anterior commissure connects two temporal lobes.
2. Corpus callosum connects right and left cerebral
hemispheres. With the growth of cerebral
hemispheres, the size of corpus callosum also
increases and it gets separated from fornix by
septum pellucidum.
3. Hippocampal (fornix) commissure: Connects right
and left hippocampus.
4. Posterior commissure is essential for light reflex
(connections not yet discovered fully).
5. Habenular commissure connects habenular nuclei
of
both sides. Habenular nuclei are part of epithalamus.
6. Optic chiasma.

Development of cerebellum
• Development of cerebellum begins on 40–45 days of
IUL.
• Two rhombic lips (right and left) appear in the
caudal
part of metencephalon.
• Initially, rhombic lips are separated by roof plate of
metencephalon.
• Later, both the rhombic lips fuse across the midline
to form cerebellar plate.

Contd.
• In 12 weeks, cerebellar plate shows a small midline
swelling called vermis and two lateral swellings
called lateral cerebellar lobes.
• A transverse sulcus separates flocculus from lateral
lobes and nodule from vermis and thus,
flocculonodular lobe arises.
• Many transverse fissures appear and give
cerebellum
its characteristic adult appearance.
• Primary fissure separates anterior lobe from middle
lobe

• Phylogenitically cerebellum is divided into
archicerebellum (older part), paleocerebellum
and neocerebellum (newest part).

Phylogenetic
part
Example Components Function
Archicerebellum Aquatic
vertebrates
Flocculonodular
lobe, lingula
Maintenance of
equilibrium
Paleocerebellum Terrestrial
vertebrates
Anterior lobe
except lingula,
pyramid and
uvula
Controls tone,
posture and
crude
movements of
limbs
Neocerebellum Higher animals Middle lobe
except pyramid
and uvula
Regulation of
fine movements
of body

• Initially, cerebellar primordium consists of outer marginal
and inner mantle zone of neuroepithelial
cells.
• Cells from mantle zone migrate through the
marginal zone to form external granular layer.
• Cells of external granular layer proliferate and migrate inward
to form cerebellar cortex.
• It consists of outer molecular layer (stellate cells and basket
cells), middle single cells layer (Purkinje cell layer) and inner
granular layer (granule cells and
• Golgi cells).
• Formation of cerebellar cortex continues from 6th month of
IUL till 1 ½ years after birth .
• Remaining cells of mantle layer (non-migrated cells) form
dentate, emboliform, globose and fastigial nuclei.
• The part of the roof plate of 4th ventricle (with pia
mater) that do not participate in the formation of cerebellum
forms superior and inferior medullary velum

Neuronal migration
• During development, neurons migrate from the
subventricular area of the brain to the surface of
the brain under the influence of glia produced
chemoattractents or chemorepellents.
• Neurons migrate approximately 2 cm to their
final destination

Stages
• Neuronal migration occurs in three stages:-
• 1. leading edge extension
• 2. Nuclear translocation
• 3. Retraction of trailing process

Leading edge extension
• It is directed by actin polymerization which is
further regulated by Rho type small GTPases
• In humans, mutation of filamin(an actin
associated protein), results In heterotropic
neurons, probably due to defective leading edge
extension.

Nuclear translocation
• It comprises of 2 sub-phases:
- centrosome positioning
- movement of nucleus towards the
centrosome
As the neurons migrate there are
major cytoskeletal alteratons in
actin and microtubule
cytoskeletons.
Microtubule appear to emanate
from centrosome just in front of
nucleus and to extend anteriorly
into the leading processes and
posteriorly to envelope the
nucleus.

Retraction of the trailing process
• At the end of migration requires integrity of the
reelin signalling pathway
• Reelin is thought to trigger recognition-
adhesiom among the target neurons.
• Other known components of the retraction of
trailing process includes member of the
lipoprotein receptor family Dab 1.

Defects of neuronal migration
• In humans , mutation in the LIS 1 or doublecortin(DCX) gene results in type 1
lissencephalies caused by defective neuronal migration during 12th to 24th week
of gestation resulting in a lack of developmental brain folds and grooves.
• Deffects of the external limiting membrane leads to the overmigration of
neurons in meninges(type 2 lissencephaly).

Refrences
• Textbook of human embryology; dr yogesh
• Neuronal Migration O Marın and G Lopez-
Bendito et al. 2007 elsevier.
• Neruronal migration during brain development,
li-huei tsai, joseph G. Gleeson, Catherine
lambert, andre G.
• Principles of neurobiology, liqun luo

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