Carpenter 3

Development of the Nervous System

Development of NS proceeds according to 2 sequences:
(a) Determination - event whereby a cell population of the embryo gives rise to cells of NS
(b) Differentiation - cellular process w/c ensures that the cells arising from the determined
population will be the source of subpopulations of neurons and glial cells that are
spec to each region
- applies to complex mechanisms whereby neurons proliferate and migrate to
appropriate locations w/in NS
- ultimately make highly specific connections with their targets
- result of interactions b/w developing neuron and its microenvironment (b/w
intrinsic and extrinsic factors)
Formation of Neural Tube
Cell division of fertilized ovum until reaching uterus
Spherical ball of cells develops a cavity, forming a blastula
Blastula becomes implanted into the uterine wall
Bilaminar layer of cells (embryonic disk) forms a few days after implantation
3rd wk of development: embryonic disk becomes trilaminar;
Notochord (mesodermal cells) lies beneath the most dorsal of ectoderm
Notochord induces ectoderm to from neural tube (primary embryonic or neural induction)
*neurulation = the response by w/c ectoderm cells is transformed into a tube
Neural induction imposes irreversible regional specificity along rostrocaudal axis of ectoderm
(forebrain, midbrain, hindbrain, spinal cord)
Late 3rd wk: formation of thickened plate of neuroectoderm (neural plate)
*neural plate = contains 125,000 cells; 50% of the ectoderm
Growth rate near margins of the plate exceeds that in the midline
(formation of a neural groove bounded on each side by an elevated neural fold)
Neural groove deepens; neural folds thicken, ultimately fuse dorsally to form neural tube
*closure of neural tube begins in the region of 4th somite (future cervical) proceeding cranially & caudally
Lumen of tube has temporary cranial and caudal connections w/ the amniotic sac:
(a) Anterior (rostral) neuropore - closes in embryos of 18-20 somites;
zone of closure lamina terminalis
(b) Posterior (caudal) neuropore - closes in embryos of 25-26 somites
*Before closure is complete, rostral portions of the neural tube are enlarged, indicating formation of
primary brain vesicles. Three primary brain vesicles are evident when closes completely form the brain
*Caudal portions spinal cord
*New somites continue to be formed in a craniocaudal sequence; end of 4th wk: 40 somites present

Neural Crest
-thinner lateral margins (neural crest cells) of neural plate that is continuous with the general body
ectoderm (lateral margins approximate as the neural folds meet and fuse)
-neural crest cells form a temporary intermediate layer b/w neural tube and surface ectoderm
Neural crest cells migrate laterally divide
Become segmented into clusters b/w tube & somites
Give rise to primary sensory neurons of dorsal root ganglia of spinal nerves
*similar clusters in hindbrain give rise to cranial nerve ganglia but not segmentally arranged
-give rise to all of the sensory cells of the PNS (few exceptions) & most of the peripheral cells of ANS
-give rise to unipolar spinal ganglion and sensory ganglia (except bipolar cells of auditory N)
-other derivatives:
(a) Neurolemmal sheath (Schwann) cells of all peripheral N
(b) Capsule cells in ganglia
(c) Sympathetic ganglia
(d) Chromaffin cells of adrenal medulla
(e) Pigment cells
Histogenesis of Neural Tube
-changes whereby columnar neuroectodem is converted to nervous tissue
-occurs in germinal zones of neural tube
-near lumen of central canal ----> ventricular system of the brain
-NE cells form pseudostrat epithelium which extends from the internal limiting mem to external
-recently closed neural tube consists of only neuroepithelial or stem cell
-wedge-shaped
-possesses cytoplasmic processes which reach internal limiting membrane
-attached to adjacent cells by terminal bars
-nuclei that divide undergo oscillatory movements (migrates to ELM then back to ILM)
-DNA replication occurs only when nucleus is near ELM (synthethic zone)
-after replication, nucleus moves toward neural tube (mitotic zone), loses contact w/ ELM
-cells undergo mitosis only when nucleus reaches innermost zone and daughter cells remain
attached by terminal bars at ILM
-after mitosis, cells elongate and migrate again toward ELM
-after several divisions, stem cells lose ability to divide (glioblasts retain mitotic capability)
-postmitotic cells leave germinal zone, migrate to appropriate position in the mantle layer
-neuroblasts send processes into outermost layer called marginal layer

Neurons
-differentiation form NE cells involves 3 phases:
(a) Proliferation and generation of specific classes
(b) Migration to specific position
(c) Maturation of cells, establishment of specific connections
Neuroepithelial cell
Glioblast
Apolar neuroblasts (neuroblasts from NE cells)
Bipolar neuroblasts
Multipolar neuroblast
Neuron
Glial Cells
-derived from NE cell
-majority are generated after production of neuroblasts has ceased
-glioblasts become spindle-shaped bipolar cells that extend entire thickness of neural tube
-large nuclei placed close to lumen; processes attached to both ELM and ILM
-some glioblasts ependymal cells
-most ependymal cells lose attachment to ELM
-line central canal and ventricular surfaces
-other glioblasts apolar or unipolar appearances astrocytes
-smaller glioblasts oligodendrocytes
-found mainly in the marginal layer
-only glial cell not derived from NE cell: mircoglia (derived from blood histiocytes)
-retain motility while neurons do not
Spinal Cord
-mantle layer gray matter of SC
-marginal layer white matter of SC
-anterior thickening of mantle layer basal plate anterior gray horn
-smaller posterior thickening alar plate posterior gray horn
-sulcus limitans = longitudinal groove that marks lateral junction of basal and alar plates
= extends length of primitive SC and continues into brainstem
= remains in the floor of 4th ventricle
-central or intermediate cells = neurons whose processes entirely confine to CNS
-association cells = neurons whose axons remain on the same side
-commissural cells = whose axons cross to the opposite side
-germinal zone diminishes in size and is reduced to a single layer of ependymal cells
Neuron Differentiation in Ganglia
-polyglonal/round cells --> spindle-shaped and bipolar --> devt of two processes:
(a) Central processes = enter SC as dorsal root fibers --> bifurcate into ascending &
descending arms which contribute collaterals to the gray matter
(b) Peripheral process
-overabundance of neuroblasts compared to # of fully differentiated ganglion cells at birth
-all cells in spinal ganglia differentiate into neuroblasts

Segmental Arrangement of Peripheral Nerve Elements

-reflex arcs consist of: afferent, intermediate, efferent neurons, & peripheral extensions
-mixed spinal nerve divides into a dorsal and ventral ramus
-also sends a fiber bundle known as ramus communicans to the sympathetic chain
-dorsal ramus = supplies muscles and skin of the back
-ventral ramus = goes to ventrolateral parts of the body wall
-four functional types of peripheral nerve fibers:
(a) General somatic afferent (GSA)
(b) General visceral afferent (GVA)
(c) General somatic efferent (GSE)
(d) General visceral efferent (GVE)
*efferent innervation of visceral differs from somatic b/c two neurons are always involved in
impulse conduction from CNS to effector organs = pre- and postganglionic fibers
*ganglion cells = # of synaptic terminals per cell may increase
# of cells innervated by a single axon decreases
Brain
-three brain vesicles in the rostral portion of neural tube:
(a) Prosencephalon (forebrain)
-lateral margins develop shallow depressions (optic sulci) ----> optic vesicle
-each optic vesicle is modified --> optic cup --> joined to forebrain by optic stalk
-shallow sulcus forms telencephalon and diencephalon
(b) Mesencephalin (midbrain)
-lumen --> cerebral aqueduct
(c) Rhomboencephalon (hindbrain)
*isthmus = constricted region b/w mid and hindbrain
-rostral portion same as caudal; w/ roof and floor plates and basal and alar plates
-two brain flexures during early embryonic stage:
(1) Cervical flexure = junction of hindbrain and SC
(2) Cephalic flexure = junction of mid and hindbrain
-6th wk: 3rd flexure (pontine flexure) develops in hindbrain, dividing it into two:
(1) Metencephalon
(2) Myelencephalon
-summary of five divisions:
(a) Telencephalon --> cerebral hemisphere, basal ganglia, lateral ventricles
(b) Diencephalon --> thalamus, hypothalamus, subthalamus, 3rd ventricle
(c) Mesencephalon --> midbrain, cerebral aqueduct
(d) Metencephalon --> pons, cerebellum, 4th ventricle
(e) Myelencephalon --> medulla oblongata, 4th ventricle