Development of the Nervous System
Neural Plate Folding
The neural plate gives rise to the CNS:
1.) invaginates along its central axis to form a neural groove and neural fold
on either side
2.) folds move together and fuses to form the neural tube (this is future brain
and spinal cord)
3.) neural tube seperates from surface ectoderm
 neural crest forms between surface ectoderm and neural tube
1.) neural crests cells migrate ventrolaterally on each side of the neural tube
-neural crest cells contribute to cranial and sensory ganglia and
nerves, medulla of adrenal gland, pigment cells
Neural Plate and Tube Formation
-neural tube  brain + spinal cord
-neural crest  PNS
-cranial (rostral) 2/3 of neural plate  brain
-caudal 1/3  spinal cord
-lumen of neural tube  ventricular system in brain
Brain Primordium
Cephalic end shows 3 dilations (primary brain vesicles):
Prosencephalon  forebrain
Mesencephalon  midbrain
Rhomencephalon  hindbrain
-cervical flexture formed between hindbrain and spinal cord
-cephalic flexture in midbrain region
*Prosencephalon gives rise to:
 telenchephalon + lateral 2 outpocketing  primitive cerebral hemispheres
 diencephalon
Mesencephalon separated from rhombencephalon by rhombencephalic isthmus
*Rhombencephalon gives rise to:
metencephalon pons + cerebellum
 myelencephalon
-neural tube consists of neuroepithelial cells
-once tube closes, cells  neuroblasts
neuroblasts form zone around epithelial layer  mantle layer  grey matter of
spinal cord
-marginal layer of spinal cord (outermost) contains nerve fibers emerging from
mantle
Neuroepithelial Cell Differentiation
Neuroepithelial cells  ependymal layer (ventricular zone)
Neuroblasts (future neurons)  mantle layer (intermediate zone)
Glioblasts (after neuroblasts)
-migrate from ventricular zone to mantle and marginal layers
Astroblasts  astrocytes
Oligodendroblasts  oligodendrocytes
Ependymal cells (after neuro/glioblasts)  ependymal lining the central canal of
the spinal cord
Microglial cells (microglia)  scattered through grey and white matter
-neuroblast become apolar, bipolar, and multipolar neuroblasts
-after production of neuroblast stops, glioblasts migrate to mantle and marginal
layers
-in mantle layer, glioblasts  protoplasmic AND fibrillar astrocytes
-in marginal layer, glioblasts  oligodendroglial cells
-later, microglia appear in CNS
-AFTER neurepithelial cells cease to generate neuro and glioblasts  differentiate to
ependymal cells
Growth Cone at the Axon Terminal
-cone growth and correct synapse occur b/c of special molecular interactions at
growth cone
-growth cone = lamellipodium + filopodia
-once target recognize, cone turns into presynaptic axon
*Axon Guidance
-axons respond to diffusible molecules for guidance
*Non-diffusible signals:
-extracellular adhesion molecules (LAMININS, COLLAGENS, FIBRONECTIN) interact
with:
1.) integrins
2.) cell adhesion molecules (CAM)
3.) Ca+-dependent cell adhesion molecules (CADHERINS)
*CADHERINS MEDIATE FINAL TARGET SELECTION AND
TRANSITION
*Diffusible signals:
1.) Chemo-attractants
-NETRINS and receptor DCC attract cone toward cue source
2.) Chemo-repellants
-SLIT and receptor ROBO prevent axon from straying back over the
midline
-SEMAPHORIN and receptor PLEXIN prevent lateral extension to nearby
axons
-Semaphorin also causes collapse of growth cones
-EPHRIN an EPH receptor
Synaptogenesis
-once axons reaches target forms synapse
1.) CADHERINS and PROTOCADHERINS mediate early synapse stage
2.) SynCAM, NCAM, NEUREXIN-NEUROLIGIN then recruited to synapse
-NEUREXIN forms presynaptic
-NEUROLIGIN forms postsynaptic
 also mediates postsynaptic density formation for NT
receptors (AMPA-R, NMPA-R)
Neurotrophic Interaction
-absence of trophic support  neurons atrophy
-autonomic glia originally innervated by several axons, input to targets decrease
until only one input remains
-NEUROTROPHINS mediate formation and maturation of neuronal circuit by:
1.) cell survival and death
2.) synapses stabilization and elimination
3.) neuronal process growth and retardation
-p75 receptor for all neurotrophins
-specific action for neurotrophin determined by:
1.) local availability of neurotrophins
2.) different combinations of receptors
3.) intracellular signaling pathways for neurons
Spinal Cord Formation
-continuous neuroblast addition to mantle  thicken ventral & dorsal sides
BASAL PLATES (ventral thickenings)  contain ventral motor horn and form
motor area
-ventral and lateral gray column
-efferent nerve group
-ventral roots of the spinal nerves
-ventral median septum/fissure
ALAR PLATES (dorsal thickenings)  form sensory area
-sensory nerve group
-dorsal gray column
-afferent nerve group
-dorsal septum
-SULCUS LIMITANS  boundary between basal and alar plates
- a group our neurons also accumulates between central and dorsal horns 
intermediate horn
Spinal Ganglia
-axons from basal plate break through marginal zone  visible on ventral side of
cord
-conduct motor impulses
-axons from alar plate break through marginal zone  ascend/descend to a higher
or lower levels
spinal ganglia form swellings on dorsal aspects  dorsal root ganglia
-two axons in dorsal root unite in T-shape
-peripheral processes of spinal ganglion pass into spinal nerves to sensory endings
in somatic or visceral structure
-central processes of spinal ganglion enter spinal cord  dorsal roots
mesenchyme surround neural tube  primitive meninx (membrane)  dura mater
(outer layer) and pia-arachnoid (inner), also called leptomeninges
-fluid-filled spaces in leptomeninges coalesce  subarachnoid space
Myelination (Myelin Sheaths)
Neural crest cells  Schwann cells
Sympathetic Nervous System
1.) neural crest cells in thoracic region migrate to either side of spinal cord
–form paired masses dorsolateral to the aorta
–connected by lilateral chain of longitudinal fibers
–ganglionated cords known as sympathetic trunks
2.) some neural crest cells migrate ventral to the aorta  preaortic ganglia
3.) other neural crest cells migrate to heart, lungs, GI  form terminal ganglia in
plexus near organs
Preganglion fibers (myelinated)
-axons of neurons in the viscero-efferent motor column
-pass through white communicating rami
Postganglionic fibers (not myelinated)
-some nerve fibers extend from sympathetic ganglia to high or lower levels in the
sympathetic chain
Gray communicating rami
-from the sympathetic chain to the spinal nerves
-from primal nerves to the peripheral blood vessels, hair, and sweat glands
Parasympathetic Nervous System
-preganglionic parasympathetic fibers arise from neurons in nuclei of brainstem and
in the sacral region of the spinal cord
-fibers from brain stem leave via CN III, VII, IX, X
-the thoracic and lumbar segments in the spinal cord are connected to the
SYMPATHETIC ganglion
Positional Changes of the Cord
-in embryo, spinal cord extends the entire length of the vertebral canal, spinal
nerves pass through intervertebral foramina near origin level
-vertebral column and dura mater grow more rapidly than the spinal cord, caudal
end of spinal cord gradually comes to lie at higher level
-in infant, spinal cord terminates at 2nd/3rd lumbar vertebra
-in adults, spinal cord terminates at the inferior border of 1st lumbar
conus medullaris- inferior end of spinal cord
filum terminale- pia mater forms a long fibrous thread
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Brian Vesicles (need to know)
Forebrain (prosencephalon)  telencephalon  cerebral hemisphere +later
ventricles
 diencephalon  thalami + third ventricle
Midbrain (mesenencephalon)  mesencephalon  midbrain + aqueduct
Hindbrain (rhombencephalon)  metencephalon  pons +upper 4th ventricle
+cerebellum
 myelencephalon  medulla + lower 4th ventricle
Myelencephalon (medulla oblongata)
-rostral part=wide and flat
-pontine flexure causes the lateral walls of the medulla to move outward and stretch
roof plate
-alar plates begin to lie lateral to basal plates
-motor nuclei begin to develop medial to sensory nuclei
-sensory nuclei in alar plate 3 groups:
1.) somatic afferent group (FROM THE EAR)
2.) intermediate special visceral group (FROM TASTE FIBERS)
3.) medial general visceral afferent group (RECEIVES IMPULSES FROM
VISCERA)
-motor nuclei in the basal plate 3 groups:
1.) medial somatic efferent group (HYPOGLOSSAL)
2.) intermediate special visceral group (BRACHIAL NERVES)
3.) lateral general visceral efferent group (VAGUS/PHARENGEAL NERVES)
Metenencephalon (pons and cerebellum)
-metencephalon also forms the cerebellum, functions as a coordination center for
posture and movement, pathway for nerve fibers between the spinal cord and
cerebral and cerebellar corticies
-pons contaisn PONTINE NUCLEI
-CEREBELLUM develops from thickenings of the dorsal parts of alar plates
Cerebellum Development
-dorsolateral part of alar plates form rhombic limbs
-vermis, small midline portion creates lateral portions
-initially has a neuroepithelial, a mantle, and a marginal layer
-cells of neuroepithelial layers migrate to surface  external granular layer
later, external granular layer migrates toward Purkinje cells  granule cells, basket
cells, and stellate cells
Mesencephalon (midbrain)
-neural canal narrows  cerebral aqueduct (connects 3rd and 4th ventricles)
-neuroblasts migrate from alar plate of midbrain (tectum) and aggregate  paired
superior and inferior colliculi
-neuroblasts migrate from basal plate  tegmentum
fibers from cerebrum  cerebral peduncles
substantia nigra  basal plate
Diencephalon
-3 swellings develop in the lateral walls of the 3rd ventricle :
 epithalamus
 thalamus
 hypothalamus
-thalamus separated from epithalamus but epithalamic sulcus and hypothalamus by
hypothalamic sulcus
-thalamic meet and fuse in midline, forming a bridge of gray matter across 3rd
ventricle  interthalamic adhesion (massa intermedia)
-a pair of mammillary bodies on ventral surface of hypothalamus
-epithalamus forms from roof and dorsal wall of diencephalon
-pineal body (gland) develops as midline diverticulum of caudal part of roof of
diencephalon
*Pituitary Glands
2 sources:
1.) upgrowth from ectodermal roof of stomodeum (Rathke’s pouch)
2.) downgrowth from neuroectodderm of the diencephalon
-adenohypophysis (from oral ectoderm)  pars anterior
 pars intermedia
 pars tuberalis
-neurohypohysis (from neuroectoderm, infndibulum)  media eminence
 infundibular stem
 pars nerveosa
-anterior lobe = pars distalis + pars tuberalis
-posterior lobe = pars intermedia + pars nervosa
Telencephalon
-continuous growth of the cerebral hemispheres in anterior, dorsal, and inferior
directions  frontal, temporal, occipital lobes
-area between frontal and temporal lobes depressed  insula
-becomes overgrown by adjacent lobes and covered by birth
-has a median part and two lateral diverticula  primordial of cerebral
hemispheres
-corpus striatum appears as prominent swelling on floor of each cerebral
hemisphere
-fibers passing to and from pass through corpus striatum  caudate and lentiform
nuclei
-hemispheres meet  longitudinal fissure
-hemispheres expand to cover diencephalon, midbrain, and hindbrain
-caudal end of each folds ventrally and rostrally  temporal lobe
Cerebral Commissures
Lamina terminalis extends from roof plate of diencephalon to optic chiasm
Anterior commissure connects olfactory bulb and related brain areas
Hippocampal commissure connects hippocampal formations
Lamina terminalis between corpus callosum and fornix  septum pellucidum
Development of sulci and gyri
-cells in the mantle zone migrate to marginal zone and become cortical layers (grey
matter)
-axons of cells in gray matter grow centrally and form white matter (medullary
center)
sulci-furrows
gyri-elevations
Congenital Malformation
Meningocele- a protrusion of the cranial meninges that is filled with cerebrospinal
fluid
Meningoencephalocele- a protrusion of part of the cerebellum that is covered by
meninges and skin
Meningohydroencephlocele- a protrusion of part of the occipital lobe that contains
part of the posterior horn of a lateral ventricle
Abnormalities of the Spinal Cord
Spina bifida occulta- located in the sacrolumbar region and covered by skin and not
noticeable on the surface
Meningocele- the meninges of the spinal cord bulge through the opening and a sac
covered with skin is visible on the surface
Meningomyelocele-the sac contains the meninges, the spinal cord, and its nerves
Myelocele (rachischisis)- the nerve tissue is widely exposed to surface