This document outlines the developmental stages of the human brain, focusing on the embryology of the central nervous system from ectodermal origins. It details the formation and differentiation of various brain vesicles, including primary and secondary vesicles, flexures, and the roles of structures like the notochord and neural crest. The document also discusses the development of specific brain regions such as the forebrain, midbrain, hindbrain, and related structures throughout early embryonic stages.

1. 1

2. 2
DEVELOPMENT OF
THE HUMAN BRAIN
Dr. Ademola A. Oremosu
Associate Professor of
Anatomy
ABUAD

3. 3
Objectives/Course Outline
 Introduction
 Primary & secondary brain vesicles
 Embryonic brain flexures
 Development of the hindbrain
 Development of the midbrain
 Development of the forebrain

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Concerning the development of the brain
• The entire nervous system is of
ectodermal origin
• By end of 3rd week, neural folds have begun to
move together & fuse, converting the neural
plate into neural tube, the primordium of the
CNS.
• Primitive streak results from proliferation &
migration of cells of the epiblast to the
median plane of the embryonic disc
• By the 18th day floor of the notochordal process
fuses with underlying endoderm.

5. 5
Secondary brain vesicles include
• Telecenphalon
• Diencephalon
• Metencephalon
• Myelencephalon
• rhombencephalon

6. 6
INTRODUCTION
Divisions of the Brain
• Forebrain, midbrain, hindbrain
• 5 major subdivisions
• Forebrain
1. Telencephalon
2. Diencephalon

7. 7
• Midbrain
3. Mesencephalon
• Hindbrain
4. Metencephalon
5. Myelencephalon

8. 8
• The entire nervous system is of
ectodermal origin, and its first rudiment
is seen in the neural groove which
extends along the dorsal aspect of the
embryo

9. 9
 Gastrulation is the process by
which the bilaminar embryonic
disc is converted into a trilaminar
embryonic disc.
 Begins with formation of the
primitive streak at the caudal end
of the embryo.

10. 10
 Primitive streak results from proliferation
& migration of cells of the epiblast to the
median plane of the embryonic disc.
 Cranial end proliferates to form primitive
node.
 Primitive groove develops in the primitive
streak.
 Primitive pit – small depression in
primitive node.
 Primitive groove & pit result from
invagination of epiblastic cells.

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16-day

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13. 13
• Some mesenchymal cells migrate cranially from
primitive node & pit, forming a median cellular
cord- notochordal/head process.
• By the 18th day floor of the notochordal process
fuses with underlying endoderm.
• Gradually the lumen of notochordal process
disappears completely.
• With further development the notochordal cells
proliferate & form a solid cord- the definitive
notochord/chordamesoderm (end of 3rd wk).
• Primitive streak undergoes degenerative
changes & disappears by the end of the 4th
week (!Sacrococcygeal teratoma ~1/35000 newborns).

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15. 15

16. 16
• As the notochord develops, the embryonic
ectoderm over it thickens to form an elongated,
slipper-shaped plate- neural plate.
• The ectoderm of the neural plate forms the
CNS.
• At first the neural plate corresponds precisely in
length to the underlying notochord.
• Neural plate appears cranial to the primitive
node & dorsal to the notochord & mesoderm
adjacent to it.
• As the notochord elongates, the neural plate
broadens & eventually extends cranially as far
as the oropharyngeal membrane.

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• Eventually the neural plate extends beyond the
notochord.
• ~ 18th day, neural plate invaginates along its
central axis to form a longitudinal median-
neural groove, that has neural folds on each
side.
• Neural folds become particularly prominent at
the cranial end of embryo & are first signs of
brain development.
• By end of 3rd week, neural folds have begun to
move together & fuse, converting the neural
plate into neural tube, the primordium of the
CNS.

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20. 20

21. 21

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Regarding the notochord
• The notochordal process and adjacent
mesoderm induce the overlying embyonic
ectoderm to form the neural plate
• As the notochordal process elongates, the
primitive streak shortens
• At end of the 3rd week the notochordal process
is transformed into notochord
• Embryonic disc is originally egg-shaped but
soon becomes pear-shaped & then slipperlike
• The notochord functions as the primary inductor
in the early embryo

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• It is a prime mover in a sries of signal-
calling episodes that ultimately transform
unspecialized embyonic cells into definitive
adult tissues & organs
• The notochord is an intricate structure
around which the vertebral column forms.
• It extends from oropharyngeal membrane
to the primitive node
• Notochord degenerates & disappears as
the bodies of the vertebrae form, but
persists as the nucleus pulposus of each IV
disc.
• Neurulation is completed during the 4th week.

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NEURAL CREST FORMATION
• As the neural folds fuse to form neural tube,
some neuroectodermal cells on the crest of
each fold lose their epithelial affinities &
attachments to neighbouring cells.
• As the neural tube separates from surface
ectoderm, neural crest cells migrate
dorsolaterally on each side of the neural
tube.
• The neural crest is eventually formed
between the neural tube & the overlying
surface ectoderm.

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26. 26

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28. 28
Derivatives of Neural Crest Cells
 Spinal ganglia (dorsal ganglia)
 Ganglia of ANS
 Ganglia of cranial nerves V, VII, IX &
X (in part)
 Neurolemmal sheaths of peripheral
nerves
 Meninges of brain & spinal cord

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Embryological Origin of the Brain
 The brain develops from the anterior end of
the neural tube (cranial to the 4th pair of
somites), which at an early period becomes
expanded into 3 vesicles, the primary
cerebral vesicles.
 These are marked off from each other by
intervening constrictions, and are named the
fore-brain or prosencephalon, the mid-
brain or mesencephalon, and the hind-
brain or rhombencephalon—the last being
continuous with the medulla spinalis.

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Secondary Brain Vesicles
 During the 5th week
forebrain partly divides into 2 secondary
vesicles- telecenphalon &
diencephalon;
Midbrain/ mesencephalon does not
divide;
hindbrain partly divides into
metencephalon & myelencephalon;
hence 5 secondary brain vesicles

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 As a result of unequal growth of these
different parts 3 flexures are formed
and the embryonic brain becomes
bent on itself in a somewhat zigzag
fashion
 The 2 earliest flexures are concave
ventrally and are associated with
corresponding flexures of the whole
head

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The first flexure appears in the
region of the mid-brain, and is
named the ventral cephalic
flexure

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 By means of the midbrain flexure, fore-
brain is bent in a ventral direction around
the anterior end of the notochord & fore-
gut, with the result that the floor of the
fore-brain comes to lie almost parallel with
that of the hind-brain.
 This flexure causes the mid-brain to
become, for a time, the most prominent
part of the brain, since its dorsal surface
corresponds with the convexity of the
curve.

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 The 2nd bend appears at the junction of
the hind-brain and medulla spinalis -
cervical flexure, and increases from 3rd
to the end of 5th week, when the hind-
brain forms nearly a right angle with the
medulla spinalis
 After the 5th week, erection of the head
takes place & the cervical flexure
diminishes & disappears.

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5th week

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 The 3rd bend is named the pontine
flexure
 Located in future pontine region; divides
hindbrain into caudal- myelencephalon &
rostral metencephalon
 It differs from the other 2 in that (a) its
convexity is forward, and (b) it does not
affect the head

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 The lateral walls of the brain-
tube, like those of the medulla
spinalis, are divided by internal
furrows into alar/dorsal &
basal/ventral laminæ

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The Hind-brain or Rhombencephalon
The cavity of the hind-brain becomes the
4th ventricle.
At the time when the ventral cephalic
flexure makes its appearance, the length
of the hind-brain exceeds the combined
lengths of the other 2 vesicles.
Immediately behind the mid-brain it
exhibits a marked constriction, the
isthmus rhombencephali.

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From the isthmus the anterior medullary
velum & the superior peduncle of the
cerebellum are formed.
The cerebellum is developed by a
thickening of roof & pons by a
thickening in the floor & lateral walls of the
metencephalon.

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The floor & lateral walls of the
myelencephalon are thickened to form
the medulla oblongata.

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The development of the medulla
oblongata
• On transverse section the
myelencephalon at an early stage is seen
to consist of 2 lateral walls, connected
across the middle line by floor- and roof-
plates
• Each lateral wall consists of an alar and a
basal lamina, separated by an internal
furrow, the remains of which are
represented in the adult brain by the
sulcus limitans on the rhomboid fossa.

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5th Week

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 The contained cavity is more or less
triangular in outline, the base being
formed by the roof-plate, which is
thin and greatly expanded
transversely.
 Neuroblasts are developed in the
alar & basal laminæ & their narrow
stalks are elongated to form the
axis-cylinders of the nerve
fibres.

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Opposite the furrow or boundary between
the alar & basal laminæ a bundle of nerve
fibres attaches itself to the outer surface of
the alar lamina -tractus solitarius, & is
formed by the sensory fibres of the
glossopharyngeal & vagus n.
 It is developed by an ingrowth of fibres
from the ganglia of the neural crest.

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• Within a few days the rhomboid lip
becomes applied to, and unites with, the
outer surface of the main part of the alar
lamina, and so covers in the tractus
solitarius & also the spinal root of the
trigeminal nerve;
• The nodulus & flocculus of the
cerebellum are developed from the
rhombic lip.

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• From the alar lamina and its rhombic lip,
neuroblasts migrate into the basal lamina, and
become aggregated to form the olivary nuclei,
while many send their axis-cylinders thru the
floor-plate to the opposite side, and thus
constitute the rudiment of the raphé of the
medulla oblongata.
• By means of this thickening of the ventral
portion, the motor nuclei are buried deeply in
the interior, and, in the adult, are found close to
the rhomboid fossa.
• This is still further accentuated: (a) by the development of
the pyramids, which are formed about the 4th month by
the downward growth of the motor fibres from the
cerebral cortex; and (b) by the fibres which pass to & from
the cerebellum.

50. 50
• On the rhomboid fossa a series of 6
temporary furrows appears- rhombic
grooves.
•They bear a definite relationship to
some of the cranial nerves; thus, from
before backward the 1st & 2nd
grooves overlie the nucleus of the
trigeminal; the 3rd, the nucleus of the
facial; the 4th, that of the abducent;
the 5th, that of the glossopharyngeal;
and the 6th, that of the vagus.

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Development of the Pons
 The pons is developed from the
ventro-lateral wall of the
metencephalon.
 The pontine flexure causes
divergence of the lateral walls of
the pons, which spreads the
grey matter in floor of 4th
ventricle.

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Development of the Cerebellum
 The cerebellum is developed in the roof
of the anterior part of the hind-brain
 The alar laminæ of this region become
thickened to form two lateral plates which
soon fuse in the middle line & produce a
thick lamina which roofs in the upper part
of the cavity of the hind-brain vesicle; the
outer surface of which is originally smooth
and convex.

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 The fissures of the cerebellum appear first
in the vermis & floccular region, and traces
of them are found during the 3rd month;
 Fissures on the cerebellar hemispheres do not
appear until the 5th month.
 The primitive fissures are not developed in the
order of their relative size in the adult—thus the
horizontal sulcus in the fifth month is merely a
shallow groove.
 The best marked of the early fissures are: (a)
the fissura prima between the developing
culmen and declive, and (b) the fissura
secunda between the future pyramid and
uvula.

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 The flocculus & nodule are developed from
the rhombic lip, and are therefore recognizable
as separate portions before any of the other
cerebellar lobules.

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 On the ventricular surface of the cerebellar
lamina a transverse furrow, the incisura
fastigii, appears, and deepens to form the tent-
like recess of the roof of the 4th ventricle
 As the cerebellar rudiments enlarge & fuse in
the median plane, they overgrow the rostral half
of 4th ventricle & overlap pons & medulla
 Some neuroblasts in intermediate zone of the
alar plates migrate to marginal zone &
differentiate into neurons of the cerebellar
cortex
 Other neuroblats from these plates give rise to
the central nuclei

56. 56
Regarding the metencephalon
 Cells from the alar plates give rise to
the pontine nuclei, cochlear &
vestibular nuclei, sensory nuclei of
trigeminal nerve

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The Mid-brain or Mesencephalon
• The mid-brain exists for a time as a thin-
walled cavity of some size, separated from
isthmus rhombencephali behind, and from
the fore-brain in front, by slight constrictions.
• Its cavity becomes relatively reduced in
diameter, and forms the cerebral aqueduct
of the adult brain.
• Its basal laminæ increase in thickness to
form the cerebral peduncles, which are at
first of small size, but rapidly enlarge after
the 4th month.

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• The neuroblasts of these laminæ are
grouped in relation to sides & floor of
cerebral aqueduct, & constitute the nuclei
of the III & trochlear n. & of the
mesencephalic root of the trigeminal n.
• By a similar thickening process its alar
laminæ are developed into the
quadrigeminal lamina.

59. 59
• Neuroblasts migrate from the alar plates
of midbrain into the tectum & aggregate to
form 4 large groups of neurons- sup & inf
colliculi
• Neuroblasts from basal plates may give
rise to groups of neurons in the
tegmentum (red nuclei, nuclei of 3rd & 4th
cranial nerves, & reticular nuclei)

60. 60
The Fore-brain/Prosencephalon
At a very early period 2 lateral diverticula,
the optic vesicles, appear, one on either
side of the fore-brain; for a time they
communicate with the cavity of the fore-
brain by relatively wide openings.
The peripheral parts of the vesicles
expand, while the proximal parts are
reduced to tubular stalks, the optic
stalks.

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5th Week

62. 62
The optic vesicle gives rise to the retina
and the epithelium on the back of the
ciliary body and iris.
The optic stalk is invaded by nerve fibres
to form the optic nerve.

63. 63
A 2nd pair of diverticula soon arise more
dorsally & rostrally- cerebral/telencephalic
vesicles- primordia of cerebral
hemispheres.
The cavities of these diverticula are the
rudiments of the lateral ventricles; they
communicate with the median part of the
fore-brain cavity by relatively wide
openings, which ultimately form the
interventricular foramen.

64. 64
The median portion of the wall of the fore-
brain vesicle consists of a thin lamina, the
lamina terminalis, which stretches from
the interventricular foramen to the recess
at the base of the optic stalk.
The anterior part of the fore-brain,
including the rudiments of the cerebral
hemispheres, is named the
telencephalon, & its posterior portion is
termed the diencephalon; both of these
contribute to the formation of the third
ventricle.

65. 65
Diencephalon
 From the alar lamina of the
diencephalon, the thalamus,
metathalamus, and epithalamus are
developed.
 Thalamus separated from
epithalamus by epithalamic sulcus &
from hypothalamus by hypothalamic
sulcus

66. 66
Thalamus
 Develops rapidly on each side &
bulges into cavity of 3rd ventricle,
reducing it to a narrow cleft
 Thalami meet & fuse in midline in
~70% of brains, forming a bridge of
gray matter across the 3rd ventricle-
interthalamic adhesion (massa
intermedia)

67. 67
Metathalamus
The metathalamus comprises the
geniculate bodies which originate as
slight outward bulgings of the alar
lamina.

68. 68
Epithamus
 The epithalamus includes the pineal
body, the posterior commissure, & the
trigonum habenulæ.
 The pineal body arises as an upward
evagination of the caudal part of roof-plate
of diencephalon, immediately in front of
the midbrian;
this evagination becomes solid with the
exception of its proximal part, which
persists as the recessus pinealis.

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In lizards the pineal evagination is elongated
into a stalk, and its peripheral extremity is
expanded into a vesicle, in which a
rudimentary lens and retina are formed; the
stalk becomes solid and nerve fibres make
their appearance in it, so that in these
animals the pineal body forms a rudimentary
eye.
The posterior commissure is formed by
the ingrowth of fibres into the depression
behind & below the pineal evagination, &
the trigonum habenulæ is developed in
front of the pineal recess.

70. 70
Hypothalamus
 From the basal laminæ of the
diencephalon the pars mamillaris
hypothalami is developed; this
comprises the corpora mamillaria &
the posterior part of the tuber
cinereum.

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The corpora mamillaria arise as a single
thickening, which becomes divided into 2
by a median furrow during the 3rd month.
The roof-plate of the diencephalon, in front
of the pineal body, remains thin and
epithelial in character, and is subsequently
invaginated by the choroid plexuses of the
3rd ventricle.

72. 72
Concerning the development of the hind-
brain in the 4th and 5th week of foetal life
• The cavity of the hind-brain becomes the
4th ventricle.
• The length of the hind-brain exceeds the
combined lengths of fore- and mid-brain.
• The anterior medullary velum and the
superior peduncle of the cerebellum are
formed from the isthmus
• The isthmus rhombencephali is located
Immediately behind the mid-brain
• Olivary nuclei are formed from neuroblasts from the
alar lamina and its rhombic lip.

73. 73
Telecephalon
• Consists of a median portion & 2 lateral
diverticulae. The median portion forms
the anterior part of the cavity of the 3rd
ventricle, and is closed below and in front
by the lamina terminalis.
• The lateral diverticulae consist of outward
pouchings of the alar laminæ; the cavities
represent the lateral ventricles, and their
walls become thickened to form the
nervous matter of the cerebral
hemispheres.

74. 74
Pituitary Gland
• The hypophysis cerebri is ectodermal in
origin
• Develops from 2 sources
• An upgrowth from ectodermal roof of
stomodeum
• A downgrowth from neuroectoderm of
diencephalon- the neurohypophysial bud

75. 75
Rhinencephalon, Corpus
triatum & Neopallium
Elliott-Smith divides each
cerebral hemisphere into 3
fundamental parts, viz., the
rhinencephalon, the corpus
striatum, and the neopallium.

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The Rhinencephalon
 The rhinencephalon represents the
oldest part of the telencephalon, and
forms almost the whole of the hemisphere in
fishes, amphibians, and reptiles.
 In man it is feebly developed in comparison with
the rest of the hemisphere, and comprises the
following parts, viz., the olfactory lobe
(consisting of the olfactory tract and bulb and
the trigonum olfactorium), the anterior
perforated substance, the septum pellucidum,
the subcallosal, supracallosal, and dentate gyri,
the fornix, the hippocampus, and the uncus.

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Corpus Striatum
 The corpus striatum appears in the 4th
week as a triangular thickening of the floor
of the telencephalon between the optic
recess and the interventricular
foramen, and continuous behind with the
thalamic part of the diencephalon
 It increases in size, and by the 2nd month is
seen as a swelling in the floor of the future
lateral ventricle

78. 78
The neopallium
 The neopallium forms the remaining, and by
far the greater, part of the cerebral
hemisphere.
 Consists, at an early stage, of a relatively large,
more or less hemispherical cavity—the primitive
lateral ventricle—enclosed by a thin wall from
which the cortex of the hemisphere is developed.
 The vesicle expands in all directions, but more
especially upward and backward, so that by the
3rd month the hemispheres cover the
diencephalon, by the 6th they overlap the mid-
brain, and by the 8th the hind-brain

79. 79
Congenital Anomalies of the Brain
• Abnormal development of the brain is
common- 3 per 1000 births
•Because of the complexity of its
embryological history

80. 80
Neural Tube Defects: Rostral
• Neural tube fails to close
• Exencephaly
• Meroanencephaly -1 /1000 births; 2-4 x in
females
– skull & brain partially or totally absent
– perinatal mortality
• Meningocele/Meningocencephalocele/Meningo
hydroencephalocele
– parts of meninges/brain/ventricular system
protrude outside skull
– mental disability depends on extent
Causative factors of NTDs
• Genetic, Nutritional, Environmental

81. 81
• Microcephaly- calvaria & brain are small;
grossly mentally retarded
• Agenesis of corpus callosum- may be
asymptomatic; seizures & mental def
common
• Hydrocephalus
• Holoprosencephaly- small forebrain, lat
ventricles often merge to 1 large ventricle
• Hydranencephaly- cerebral hemispheres
are absent/represented by membranous
sacs
• Arnold-Chiari Malformation- 1/1000 births

82. 82
• Mental Retardation- from chromosomal
abnormalities/ mutant gene
•Maternal alcohol abuse is the
commonest cause of mental
retardation
• Congenital anomalies of brain may be
caused by alterations in morphogenesis or
histogenesis of the nervous tissue or from
developmental failures

83. 83
• Abnormal histogenesis of cerebral cortex
can result in seizures & various degrees of
mental retardation
• Submental intellectual development may
result from exposure of embyo/foetus
during 8- to 16-week period of
development to certain viruses & high
levels of radiation
• Prenatal factors may be involved in the
development of cerebral palsy

84. 84

85. 85
Essay 1
• A) What is the incidence of congenital
abnormalities of the brain and why are
they common.
• B) Discuss the morphogenesis and
implications of 6 congenital abnormalities
of the brain.

86. 86
Essay 2
• With the aid of well-labeled diagrams,
describe the embyology of the fore-brain

87. 87
Stages of Cellular Activity
• 6 distinct stages
1. Neurogenesis
2. Cell migration
3. Differentiation
4. Synaptogenesis
5. Neuronal cell death
6. Synaptic rearrangement ~

88. 88
Stages of Cellular Activity
1. Neurogenesis
– mitosis
– nonneural cells
neurons do not divide
– develop into neurons or glia
glia produced throughout life ~

89. 89
Stages of Cellular Activity
2. Cell migration
– to specific “brain”
locations
– along radial glia
– later: along other
neurons ~

90. 90
Stages of Cellular Activity
3. Differentiation
– into specific neuron types
– by induction
influenced by surrounding cells
– or cell-autonomous ~

91. 91
Stages of Cellular Activity
4. Synaptogenesis
– formation of synapses
– growth of axons &
dendrites
growth cones
– neurotrophic factors~

92. 92
Stages of Cellular Activity
5. Neuronal cell death
– apoptosis: programmed cell
death
– 20-80% of neurons in a
region
– genetically programmed
– lack of neurotrophic factors ~

93. 93
Stages of Cellular Activity
6. synaptic rearrangement
– elimination of synapse
– formation of new synapses
– dependent on neural activity ~

94. 94

95. 95

96. 96