Levels of Neural Differentiation
• ORGAN
macroscopical changes in the neural tube
(hemispheres, ventricles)
• TISSUE
functional regions form in the wall of the neural tube
(motor, sensory, autonomous)
• CELLULAR
Different neuronal and glial types differentiate
(histogenesis)
Milestones in Neural Tissue Differentiation
INDUCTION (chorda dorsalis ) - neuroectoderm
NEURULATION formation of the neural tube
PROGENITOR CELLS form in the neural tube
PROLIFERATION and DIFFERENTIATION of the progenitors
•Neurone
•Glia
MIGRATION, AXONAL GROWTH
Formation of SYNAPSES (communication between distant cells)
Primary Neurulation
Neural induction and neurulation
Specification of neural fate and
formation of the neural tube.
NEURAL INDUCTION : the
delineation of ectodermal cells to
the neural fate
NEURULATION: the process in
which the ectoderm of the future
brain and spinal cord - the neural
plate – develops, folds and forms
the neural tube
Primary Neurulation
Induction of the Neural Tube
epiblast inhibition of
default
inhibition of BMP-2
activin
default BMP-4
mesoderm epidermis
follistatin
pathway
default
chordin
noggin (BMP-
E-cadherin
inhibition)
neural tube
N-Cadherin
Numerous signal proteins inhibit the activity of
BMP/Activin, thereby maintaining the default mechanism
( neural tube )
Closure of the
neural tube in a
„zip-lock” like
manner
© 2005 Elsevier
)
Secondary Neurulation (described in avian embryos)
fusion
cavitation
D 27
Below S2
eminentia
caudalis
neural tube
Spinal Cord Development External
limiting
membrane
Composition of Neural Tube
Internal limiting membrane Neuroepithelial cells
Sclerotomal somitic mesoderm
Differentiation in the Wall of the Neural Tube
The wall of a recently closed neural tube
consists of neuroepithelial cells
(pseudostratified epithelium)
Once the neural tube closes, neuroepithelial
cells begin to give rise to primitive nerve
cells, or neuroblasts forming the mantle
layer.
The outermost layer of the spinal cord, the
marginal layer, contains nerve fibers
emerging from neuroblasts in the mantle
layer
Development of the Spinal Cord
(cell body; grey matter) (axon rich; white matter)
Development of Spinal Cord
Neurogenesis
Neuroblasts have a central process
extending to the lumen (transient
dendrite), but when they migrate into
the mantle layer, this process
Neuroepithelial cells
disappears, and neuroblasts are
temporarily round and apolar. With
further differentiation, two new
cytoplasmic processes appear on
Bipolar neuroblast
opposite sides of the cell body,
forming a bipolar neuroblast
(primitive axon, primitive dendrites)
The cell is then a multipolar
neuroblast and with further
development becomes a neuron
Multipolar neuroblast
Development of Spinal Cord
Gliogenesis
Glioblasts migrate from
the neuroepithelial layer
to the mantle and
marginal layers
In the mantle layer they
differentiate into
protoplasmic and
fibrillar astrocytes
In the marginal layer
oligodendroglial cells Later a third type of supporting cell, the
differentiate. This cell microglial cell, appears in the CNS. This
forms myelin sheaths highly phagocytic cell type is derived from
around the ascending and vascular mesenchyme when blood vessels
descending axons grow into the nervous system
Spinal Cord Development
A. Marginal Zone
1. Derivative of neural tube
2. White matter portion of central nervous system
B. Alar plate
1. Derivative of neural tube
2. Portion of central nervous system
3. Associated with afferent (sensory) function
Intermediate zone
C. Basal plate
1. Derivative of neural tube
2. Portion of central nervous system
3. Associated with efferent (motor) function
D. Sulcus limitans (between B and C)
1. Derivative of neural tube
2. Portion of central nervous system
3. Separates alar plate from basal plate
Development of Spinal Cord
Compartmentalisation and Organization
roof
alar plate
dorsal horn
(sensory
Central canal interneurons)
sulcus limitans
lateral horn
intermediate zone (grey substance) (autonomic nuclei)
ventricular zone (ependyma)
ventral horn
(motor neurons)
marginal zone (white substance)
basal plate
Pax-6 commissure
floor plate
Above the Sulcus Limitans
A. Dorsal Columns
1. Derivative of alar plate (neural tube)
2. Portion of central nervous system
3. Neurons in the dorsal columns constitute afferent nuclei
B. Dorsal rootlet
1. Derivative of neural crest
2. Portion of peripheral nervous system
3. Composed of Schwann cells and cell processes for sensory
neuroblasts in spinal (dorsal root) ganglion
C. Afferent sensory neuroblasts in spinal (dorsal root) ganglion
1. Derivative of neural crest
2. Portion of peripheral nervous system
3. Associated with afferent (sensory) function
Below the Sulcus Limitans
A. Ventral Columns
1. Derivative of basal plate (neural tube)
2. Portion of central nervous system
3. Neurons in the dorsal columns constitute efferent nuclei
B. Lateral Columns
1. Derivative of basal plate (neural tube)
2. Portion of central nervous system
3. Neurons in the lateral columns constitute efferent nuclei
C. Ventral roots of spinal nerve*
1. Derivative of neural tube
2. Portion of central nervous system
3. Cell processes for motor neuroblasts in ventral horn
Spinal Cord Development
Afferent sensory Sulcus
neuroblasts Marginal Zone
limitans Roof Plate
Dorsal column
Afferent
sensory
Lateral
neuroblasts column
in spinal
ganglion
Dorsal
Efferent motor root of
neuroblasts spinal
nerve
Floor Plate Ventral column
Ventral root of spinal nerve
Compartmentalization of the Spinal Cord
Development of Spinal Nerves
Dorsal root ganglion Axons of the dorsal root
multipolar
Axons of the ventral root
Motor nerve fibers begin to appear in the 4th week, arising from cells in the basal
plates. These fibers collect into bundles - ventral nerve roots
Dorsal nerve roots form cells in dorsal root ganglia (spinal ganglia). Central
processes form bundles that grow into the spinal cord opposite the dorsal
horns. Distal processes join the ventral nerve roots to form a spinal nerve
Almost immediately, spinal nerves divide into dorsal and ventral primary rami.
Dorsal primary rami innervate dorsal axial musculature, vertebral joints, and the skin
of the back. Ventral primary rami innervate the limbs and ventral body wall and form
the major nerve plexuses (brachial and lumbosacral).
Development of Spinal Nerves
Schwann cells myelinate the peripheral nerves with each cell myelinating only a single
axon. These cells originate from neural crest, migrate peripherally, and wrap
themselves around axons, forming the neurilemma sheath
Beginning at the 4th month of fetal life, many nerve fibers take on a whitish appearance
as a result of deposition of myelin, which is formed by repeated coiling of the Schwann
cell membrane around the axon.
The myelin sheath surrounding nerve fibers in the spinal cord has a completely different
origin, the oligodendroglial cells. Unlike Schwann cells, a single oligodendrocyte can
myelinate up to 50 axons.
Nerve Fiber Coverings
Schwann cell nucleus (PNS)
Oligodendrocyte nucleus (CNS)
Basement membrane
Nerve
fiber
Unmyelinated axons
Each Schwann cell is able to
house multiple axons
occupying invaginations of Myelinated axon
its cytoplasm. Multiple wrapping of
Schwann cell plasma
membrane (“jelly - roll”)
around single axon.
Myelination of Nerve Fibers
• Myelin sheaths surrounding nerve processes in the CNS
– Begin to form during the late fetal period
– Continue during the first postnatal year.
– Formed by oligodendrocytes
– Derivative of neuroepithelial cells
• Myelin sheaths surrounding nerve processes in the PNS
– Begin about 20 weeks gestation
– Continue till puberty
– Formed by Schwann cells
– Derivative of neural crest
– Motor roots are myelinated before sensory roots
Positional Changes in the Spinal Cord
w 24w newborn adult
Molecular Events
Dorsal and ventral regions of the developing spinal cord are
dependent upon concentration gradients between members of the
transforming growth factor beta (TGF-b) family of growth factors
secreted in the dorsal neural tube and sonic hedgehog (SHH) secreted
by the notochord and floor plate.
Initially BMP 4 and 7 are secreted by ectoderm overlying the neural
tube, then, BMP4 induces a cascade of TGF-b proteins, including
BMP5, BMP7, activin, and dorsalin in the roof plate and surrounding
area. As a result, cells near the roof plate are exposed to the highest
concentrations with more ventrally positioned cells seeing less and
less of these factors.
Similar events occur in the ventral region of the neural tube, only the
signaling molecule is SHH. This factor is first expressed in the
notochord followed by the establishment of a second signaling center
in the floor plate. As a result, there is a diminishing concentration of
SHH from the ventral to the dorsal region of the neural tube. These
gradients then activate transcription factors that regulate
differentiation of sensory and motor neurons.
DEVELOPMENTAL MALFORMATIONS
