perspective Developmental on organization of
the nervous system
Why do we divide the brain into three major
subdivisions (forebrain, midbrain, and
hindbrain)?
How are the dividing lines between the three
divisions set?
Why is the forebrain subdivided into the
telencephalon and diencephalon?
The answers come from the organization of
the nervous system very early in its
development.
human
brain
is really
just ....
a folded
tube.
1
Early differentiation of the nervous system
in a vertebrate embryo
Development of the brain at the anterior end of
the neural tube
2
Development of the
telencephalon
Developmental
expansion of the
telencephalon is
reflected in the shape
of the lateral ventricles
Note that the continuity
of the ventricles and
spinal canal points out
the underlying form of
the human brain as a
contorted tube
3
Development of the nervous system can be
divided into four broad stages
1. Neurogenesis: cells that will ultimately become
neurons must divide and proliferate to produce
the necessary precursor cells (the cellular raw
material of the nervous system)
2. Neuronal migration: the newly produced
neurons must move from their birthplace to their
appropriate locations within the nervous system
3. Process outgrowth: the cell body of the neuron
must grow dendrites to receive inputs from other
neurons and an axon to connect with the
appropriate targets
4. Synapse formation: after the axon has reached
the target, it must recognize the correct target
cells and form synaptic connections
Neurogenesis: first
step is Neuronal
Determination
Neural induction: nervous
system arises during
gastrulation from a portion
of the ectoderm called the
neuroectoderm
Mesodermal cells that form
the notochord send a
signal to the overlying
ectodermal cells, inducing
them to form the neural
plate
The part of the dorsal lip of
the forming mesoderm that
is capable of inducing the
neural plate is called the
Spemann organizer
4
Gastrulation
movie
Xenopus laevis
Vegetal View of
Gastrulation &
Neurulation:
(15.0 hours
elapsed, 48
minutes/
second).
Neurogenesis: the
next step is neuronal
proliferation
At early stages of
development, the neural
tube consists of only two
layers: the ventricular
zone, where cells divide,
and the relatively cell-free
marginal zone.
After division, daughter
cells can either remain in
the ventricular zone and reenter cell cycle, or migrate
out to take their position in
the developing brain
5
Proliferation and migration
www.current-biology.com/cgi/content/full/17/2/146/DC1/
Neuronal migration: follow
the radial glial cell road
t early stages, cells of the deep
A
cerebellar nuclei form first and
take up their positions
urkinje cells are born later and
P
must migrate past the deep
nuclei to form the outer part of
the cerebellum
he Purkinje cell precursors
T
follow along special glial cells,
the radial glial cells, to reach their
destination.
6
Process
Outgrowth
Purkinje cell
ollectively,
C
dendrites and
axons are called
neurites
t the leading
A
edge of a
growing neurite
is the growth
cone
ow do growth
H
cones navigate
to their correct
location?
Growth cones must be able to adhere to the substrate on which they are growing.
dhesion is carried out by cell adhesion molecules in the membrane of the growing
A
neurite
wide variety of different cell adhesion molecules exist, but a particular neuron
A
expresses only a specific subset during neurite outgrowth
o, a neuron can interact with and grow on some substrates but not others, whether depending
S
on the substrate has adhesion molecules that are complementary to the
neurons cell-surface molecules
7
In vivo axon pathnding
motor neuron
8
Families of cell adhesion molecules
dhesion can be mediated by cell-to-cell interactions (as with the
A
neuron/radial glia interaction) or by interactions between the growth
cone and the extracellular matrix
he extracellular matrix (ECM) is a ubiquitous extracellular substrate
T
found in almost all tissues. It is secreted by the cells that make up the
tissue.
he structural backbone of the ECM consists of collagen, which
T
is a protein, and glycosaminoglycans, which are large
polysaccharide molecules that often combine with proteins to form
proteoglycans
he ECM also contains fibronectin and laminin, which are
T
glycoproteins that promote adhesion, and tenascin, which is a
glycoprotein that can either promote or inhibit neurite adhesion,
depending on the type of neuron
he partner proteins on cells that interact with the molecules of the
T
ECM are the cellular adhesion molecules, which are divided into
four families of proteins: integrins, cadherins, selectins, and the
immunoglobulin family
9
The Complex Family of Integrins
ntegrins are formed by two
I
protein subunits, and
everal types of both and
S
subunits exist and can
associate in various
combinations to form over 20
different integrins
ach of the integrin subtypes
E
binds a particular subset of
complementary adhesion
molecules in the ECM
10
The Immunoglobulin Family
he immunoglobulin family
T
includes N-CAM (neuronal cell
adhesion molecule) and NgCAM (neuronal-glial cell
adhesion molecule)
he molecules are involved in
T
cell-to-cell adhesion, rather than
cell-to-ECM interactions
dhesion molecules of the
A
immunoglobulin family bind to
molecules of the same type on
neighboring cells
Chemotropic Molecules and Neurite Guidance
ovements of growth cones are also
M
guided by chemotropic molecules,
which are released into the
extracellular space and diffuse some
distance to affect growth cones
hese signal molecules either attract
T
growth cones (chemoattractants),
causing them to turn toward the
source, or repel growth cones
(chemorepellents), causing them to
turn away from the source
ells that release chemotropic
C
molecules can serve as guideposts or
beacons for the navigation of nearby
growth cones
n example of a chemotropic
A
molecule is semaphorin III. The
netrins are another family of
chemotropic molecules
11
Synapse Formation: The Neuromuscular Junction
fter growth cones of motor neurons
A
have successfully navigated to their
target muscle, they must form
synapses with the muscle cells
rowth cones stop when they
G
encounter muscle cells and transform
into synaptic terminals
he neurotransmitter released by
T
vertebrate motor neurons is
acetylcholine (ACh)
ontact of the synaptic terminal
C
induces clustering of ACh receptors in
the muscle cell at the site of contact
hat is the molecular basis of this
W
clustering?
Mechanism of ACh Receptor Clustering
he synaptic terminal of the
T
motor neuron secretes agrin
into the synaptic cleft, where
it binds to the ECM (called
the basal lamina in the
muscle)
grin interacts with
A
dystroglycan in the
membrane of the muscle cell
ystroglycan is attached to
D
the cytoskeleton of the
muscle cell by means of
dystrophin
he dystroglycan/dystrophin
T
complex recruits rapsyn,
which in turn binds to ACh
receptors, anchoring them at
the site of synaptic contact
12