Download Development of the CNS - Yeasting

©2009 Mark Tuttle
Development of the CNS – Dr. Yeasting
- Ectoderm
o Neuroepithelium
 Becomes central portion of nervous system
 All the cells which have their cell bodies within central portion of nervous
system, EXCEPT MICROGLIAL CELL
 Don’t come in at all until invasion of vasculature
 i.e. they come in with mesodermal ingrowths
 Take up residency within neural tube, and take up phagocyticic function
 Is multipotential
 Differentiate into:
o Glial cells (almost all)
 Oligodendrocytes
 Astrocytes
 Fibrous
o Stronger, have intracellular fibers within
them
o Are more supportive
o Found largely within tract areas
 Protoplasmic
o Help line blood brain barrier
 Radial (temporary)
 Ependymal cells
o Line central canal and ventricles
o Helps produce CSF!
o Extend from luminal surface to pial
surface
o Neural cells (almost all)
 EXCEPT mesencephalic nucleus of CN V
 These are thought to be neural crest cells that
didn’t separate away like other primary sensory
neurons did, but instead got embedded in
mesencephalon
o Transition tissue
 Neural crest
 Primary sensory neurons
 Postganglionic autonomic neurons
o Including adrenal medulla
 Melanocytes
 Schwann cells
©2009 Mark Tuttle
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In head/neck region, gives rise to CT structures, especially supportive
tissues
o Ex. Cartilage and bone
More caudally, does NOT give rise to CT elements, but gives rise to the
other stuff listed above
Mesoderm
o Somites
 Axial skeleton
o Intermediate
 Genital system
o Lateral plate
 Digestive system
 Body wall
Endoderm
Notocord
o Not only a skeletal element (nucleus pulposis)
o Strong controller, inducer, regulator
 Does NOT activate ectoderm to become neuroepithelium
o Will elaborate
o Diffuse in embryonic mass, help create 3-4 dimensional matrix, signaling where cells are
within embryonic body
Procordal plate (cranial to the notochord)
o Around the oropharyngeal membrane
o Sends out many signal molecules and is responsible in the short run to help control
development of cranial regions whereas the notochord is responsible to help develop
non-cranial portions of body
o When you get into neck region, there is a “border” where it transitions from
procordal/notochord control
o Possible do develop a fetus with perfectly good body, but messed up cranium because
procordal plate had a problem
Spinal cord & lower brainstem have a similar (not exactly the same) structure, but once you get
above that: diencephalon & telencephalon, the organization changes
o Reason: notochord controls development up to the junction between
midbrain/diencephalon
o Above this level, it is under control of procordal plate
Neural plate:
o cells here assume a columnar epithelial configuration
o elsewhere, regular ectoderm, are cuboidal
o There is a transition tissue between regular ectoderm and neural plate
 Neural crest!
o Undergoes folding process, and gives rise to neural groove
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Margins of the plate begin to rise up
Changing from relatively flat structure to a trench (if you will)
As the neural groove forms, the neural crest which was at the margin, is now
brought closer together, sealed off with [roof plate]?
 Regular ectoderm is brought closer together
 Neural groove ultimately closes on its dorsal aspect and gives rise to neural tube
 As this closure occurs, neural crest cells migrate downward and ultimately lie
lateral to neural tube
 Now, neuroepithelium comprises the neural tube
 Fusion of the tube usually begins in region that usually becomes the neck
region, and “zippers” both ways, cranially and caudally
 As neural groove is closing, ultimately the ends of the neural tube will still be
open (openings = neural pores)
 Ultimately cranial/caudal neural pores will ultimately close.
 Day 24 for cranial, day 26 for caudal
 α-fetal protein is produced by neural crest area
 Does not normally get out of embryonic system
 But if there is a defect and it escapes via neural pores or some other
hole within neural tube, α fetal protein builds up in amniotic fluid and
gets into maternal circulation
 This is often tested in pregnancy
 If found positive, further testing is necessary to see if there are neural
tube defects
 Not much can be done, but can forewarn parents-to-be
Adjacent to the neural tube are developing somites
o Develops into
 Base of skull
 Vertebral column
 Musculature of axial skeleton, limbs
 pharyngeal arches
 Part of CT of dermis
o Partially controlled by neural tube
o Also reciprocally influences development within neural tube
Tissue surrounding somites will migrate upward and fill in region around neural tube
Timing is important
o If delayed closure of neural tube, tissue surrounding it (somites) tissue may no longer
“be in the mood” to migrate since it’s on its own timer
o Differential growth and differential tensions can pull ectoderm apart, even pull open the
neural tube (Myeloschisis = open tube)
o If you have some tissue migrating, but not really enough to make a full vertebral column
 Spina bifida
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Neural arch is not complete
Can get protrusion of tissue through here of vesicle
 Meningocele
 Meningomyelocele (not only meninges, also neural tube – myelon –
spinal cord)
Dorsal vertebral column defect
o Lack of portion of neural arch: lamina, spinous process, or more extreme: non closure –
neural tube is not closed and is continuous with surface epithelium
o Under modern circumstances, closed defects (spina bifida cystic with meningocele) can
live productive lives
o Open defect, however, no way of closing it. Infection sets in very quickly, and child dies
of overwhelming infection of nervous system
Sides of neural crest
o Becomes DRG
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Development of neuroepithelium
 In inactive stages of mitotic cycle, developing neural cells out toward periphery
 In mitotic phase, they are down toward lumen
 Mostly, running from luminal to pial surface
 See a migration of nucleus within cell, not whole cell
 Luminal aspect is the generative aspect
o Combine concept of development (luminal to pial) with radial cells
 Radial cells are important in areas of nervous system that are stratified
 Ex. cerebral cortex.
 Neurons proliferating near luminal surface
 Neuroblasts round up and migrate up radial glial cells
nd
o 2 wave migrates up and goes through existing layer to reach outer surface
o In neocortical layer, (six layers), occurs several times
 This probably also happens in allocortex, but not as many times
o Develop into cortical column
 All cells in a given column migrated in a proliferative zone out to the pia and are
organized in a “family”
o Oldest neurons are the innermost (layer 6), because subsequent layers LEAPFROG older
layers
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Neural tube
o Neural tube gets stratified
o In early neural tube, there are 3 major zones
 Neuroepithelium (ventricular zone) right next to lumen
 Proliferative, reserve cell zone
©2009 Mark Tuttle
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Mantle zone (intermediate): Cells which have migrated toward periphery
 Develop processes, spread throughout nervous system
 Becomes the “Honda H” of the spinal cord – grey matter
 Marginal zone: on periphery where processes of Mantle zone cells develop
 Becomes white matter of spinal cord
o Ventral/Dorsal  afferent/efferent organization develops
 Develops because of signaling factors
 Mantle
 Notocord, ventrally, realeases SHH which signals that this area is ventral
and should develop efferent neurons (basal plate)
o Highest concentration of SHH yields lower motor neurons (send
axons out of CNS to innervate skeletal muscle)
o Adjacent to them (slightly lower concentration) develop into
other motor neurons, gamma and beta
 Dorsally, signaling factors, including bone morphogenic factors, PAX
genes signal this as dorsal, should develop afferent neurons (alar plate?)
o Most dorsally, highest exposure to PAX/morphogenic factors
develop into 2nd order relay afferent neurons
 Intermediate zone develops in between these two zones
 Sulcus limitans
o Medial sulcus is in middle
o Neural crest cells
o Origin of neuroepithelium
 Notocord does NOT activate ectoderm to develop into neuroepithelium
 Instead, signaling molecules from notochord influence neural tube
 Releases chordin and noggin, released into intercellular space
o Interact with bone morphogenic proteins and other
transforming growth factors and prevent them from making
their way to the ectoderm
o Thus, this ectoderm is then free to differentiate into
neuroepithelium
o THUS, neuroepithelium is really the default tissue of ectoderm,
but it usually is acted on by bone morphogenic/other
transforming growth factors to develop into neuroepithelium
IGNORE OBJECTIVE #14
Disorders of Neural crest cell
o Congenittal megacolon
o Waldberug’
 White forlock
 Related to neural crest cells, both bigment within regular hair cells and ear hair
cells because it usually helps generate endolymph there
©2009 Mark Tuttle
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 Results in deafness
o Albinism
 Melanocytes – neural crest
o Feto Chromatosis
 Excess adrenaline etc because of
o Neuro fibratosis
 Combination of problems of dermis and neural supportive tissue
o DeGeorge syndrome
 Gets more into CT elements
 BVs, septation of the aorta
Differential growth of spinal cord
o Spinal cord initiall is down low
o Spinal cord grows slower than vertebral column
o DRGs and nerves stay put and elongate to form cauda equine
Divisions
o Telencephalon
o Diencephalon
o Mesencephalon
o Rhombencephalon
 Metencephalon
 Cerebellum
 Pons
 Myelencephalon
 Medulla
Nerves grow out and try to make contact with peripheral tissues
o If they indeed make contact, they become mature nerves
o If they only make it to for example a muscle which is already innervated, they die off
 Ex. Basal plate (ventral area)
 This explains differential gray matter in different sections of spinal cord
Folding of embryo
o Neural tube gets bent as head forms
o Caudal to notochord  No more basal plate (motor neurons)
o Develop mesencephalic flexure -> main brain flexure
o Develop Rhombencephalic flexure
o Develop cervical flexure
o All balance out
Cerebellum formation
o Thin tissue layer between ventricle in 4th ventricle
 Just Epyndyma
 Tila choroidia forms median aperture madidiga
 Also forms lateral apertures of luschka
©2009 Mark Tuttle
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Granular cells
 Granular cells on surface
 Cell body migrates inward
 Become parallel processes which interact with purkinje cells
o Deep nuclei are a later migration from ventricular zone
 Ex. Dentate nucleus
o NOT complete at birth
Brainstem
o Under control of homeobox genes (also control pharyngeal arches nearby)
 Determine structure of pharyngeal arches and neurons which go into
pharyngeal arches
o Basal plate
 Separates into CN nuclei
 CN III, VI, XII
 Special visceral efferent (skeletal mm of pharyngeal origin)
 V, VII, IX, X (nucleaus ambiguous)
 General visceral efferent (preganglionic parasympathetic)
 Edinger westval
 Salivatory
 Dorsal motor nucleus of vagus
o Alar plate
 Special visceral afferent
 Solitary nucleus
o VII, IX, X
 Vestibular cochlear
o VIII
 General somatic
 V
 Reticular nuclei
 Not just neurons that receive info from primary sensory neurons, but ALSO all
the interneurons
Diencephelon/telecephalon which were initially separate, fuse
o Telencephalon
 Basal ganglia
 Medial temporal lobe
 “older” areas of cortex
 Cortex
 Processes leaving/entering cortex, cut through the nuclear groups and create
striatum, separate – and create:
 Caudate nucleus
 Putamen
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Held together by three commissures
 Anterior
 Hippocampal
 Corpus callosum
 All start out in the area known as the lamina terminalis
o Was the anterior aspect of the neural tube
o Anterior wall of the third ventricle
 Oldest commisure is the anterior commissure
o Connects largely olfactory areas
 Hippocampal commissure connects the two hippocampal formations
o They were initially very anterior, but migrated posteriorly
 Corpus callosum
o Starts in close proximity to lamina terminalis
o Begins to knit together frontal lobe structures and then
progressive posteriorly, knitting together structures as it goes
o Of these areas, corpus callosum is the most common area for
problem
 Tissue between corpus callosum and fornix gets stretched out and
becomes septum pellucidum
Ventricles
 Choroid outside
 Tila choroidia inside
 BVs of pial origin invaginate into tila choroidia
o Becomes choroid plexus
o Creates component of CSF
o Choroid epithelium is the main filter determining what gets out
into CSF
o Presence of healthy astrocytes induces blood brain barrier to
develop
o If you don’t have astrocytes, you don’t get a blood-brain barrier
 Not just development, also postnatal life
o In tila choroidia, there are no astrocytes, do not get blood brain
barrier
 Disorders
o Blockage within ventricular system
 Get hydrocephalus
 Should not really see this in developed countries
 Can put a shunt in here to correct this
Head growth
 Mostly occurs after birth
©2009 Mark Tuttle
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Resistive pressure of uterus is removed when baby is born head can
now grow