Development of CNS Flashcards
By the end of development, what structures does the ectoderm gives rise to?
– the central nervous system (CNS)
– the peripheral nervous system (PNS)
– the sensory epithelium of the ear, nose and eye
– the epidermis, hair and nails
– the subcutaneous, mammary and pituitary gland
– the enamel of teeth
Describe development of the notochord
From the primitive node, The notochord extends under the ectoderm in the opposite direction to the primitive
streak, this first forms the axial process, then the notochordal process and then finally the
notochord
what patterning structure does notochord development follow and what does this allow notochord to do
Transient patterning structure
- role in molecular signalling
- direction of embryonic folding
The notochord has an inductive relationship with the _________
overlying ectoderm
how is formation of neural plate induced
Appearance of the notochord and mesoderm induces the overlying ectoderm to thicken and form the neural plate- beginning of development of the nervous system
what do cells of the neural plate form
Cells of the plate make up the neuroectoderm:
initial event in the process of neurulation (neuraltion is transofrmation of neural plate into neural tube)
How does the neural plate becomes neural tube (neuralation)
• Neural plate Lengthens and lateral edges elevate- Forming the neural folds
– Depressed midregion forms the neural groove
- cells become columnar in apperance
• The folds approach each other in the midline and fuse- Forming the neural tube
Bending of neural plate depends on a number of factors.Name these intrinsic and extrinsic factors and hinge points
• Intrinsic factors – Cytoskeleton – Stage of cell cycle • Extrinsic factors – Adhesion points e.g. within notochord, surface ectoderm
o Hinge points:
Median hinge point – MHP => allows the neural tube to be pulled down
- Attached to the notochord
- Cells become wedged
Dorsolateral hinge point – DLHP
- Cells become wedged => allow fusion by convergence
what causes induction of the neural plate
- Up regulation of FGF
- inhibition of BMP-4
Need both of these to cause induction
How does inhibition of BMP-4 occur
- Chordin: BMP-4 antagonist
- Noggin: inactivates BMP-4
Neural plate switches from E-cadherin to _______ expression and what does this allow
N-cadherin
This allows the two neural folds to join and prevents fusion of neural tube to the overlying ectoderm
when does gastrulation occur and what happens
- Occurs in week 3
Cells from the bilaminar disc through migration and differentiation of cells forms the trilaminar disc (the three germ layers):
o Ectoderm
o Mesoderm
o Endoderm
The migration of cells from the bilaminar disc also gives rise to other important structure, what are these?
o Primitive streak
o Notocord – mesodermal origin
o Neural Plate which forms the neural tube
what are the population of cells that are found at the lateral border of the neural tube called?
Neural crest cells
describe the fate of the neural crest cells (how they travel to underlying mesoderm)
- NC cells dissociate from their neighbours and undergo an epithelial to mesenchymal transition and leave the neuroectoderm by active migration and displacement
- The cells leave the neuroectoderm soon after the closure of the neural tube via pores in the basal lamina
- This starts in the trunk region of the embryo
- Enter the under lying mesoderm
what do NC cells give rise to
- Ganglia
o Schwann cells
o Adrenal Medulla – trunk neural crest cells
o Melanocytes and hair follicles – from trunk neural crest cells
o Connective tissue in head region – cranial neural crest cells – these cells also give rise to the melanocytes and hair follicles in these regions – HNN regions mainly
Disruption of neural crest migration can result in malformations. Name and describe these malformations
1) Treacher Collins syndrome
- Under development of zygomatic bones and ears
- Distinct facial features and loss of hearing
- Mutation in the TCOF 1 gene- Retinoic acid exposure can cause this
2) Di George Syndrome (22q11.2 deletion syndrome)
- Cleft palate
- Cardiac abnormalities
- Abnormal facies
- Thymic aplasia
what direction does the closure of the tube occur
fusion begins in cervical region (neck) and proceeds in cephalic and caudal directions.
what do the open ends of the neural tube form and what are they connected with
anterior neuropore
posterior neuropore
Connected with the overlying amniotic cavity
when does neural tube closure occur
closure occurs in week 4
when do anterior and posterior neuropore close
anterior - day 25
posterior- day 27
what do walls of the closed neural tube contain and what do these cells give rise to
Neuroepithelial cells
Give rise to neuroblasts
what is the histology of neuroblasts
- large, round nuclei
- pale nucleoplasm
- dark staining nucleolus
Neuroblasts form 2 layers, what are these layers called and what do they form in relation the spinal cord
The Mantle layer – inner layer
- forms the grey matter of the spinal cord
The Marginal layer- outer layer
- Contains the projections (nerve fibres) emerging from the neuroblasts in the mantle layer
- Myelination of these nerve fibres occurs which forms:
white matter of the spinal cord
wall of neural tube differentiates. what does this result in
Thickening of ventral and dorsal aspect
what is thickening of ventral and dorsal aspect called and what do they contain
ventral thickening- Basal plate: contains the ventral MOTOR horn cells
Dorsal thickening- Alar plate: contains the sensory area of spinal cord
what is sulcus limitans
marks the boundary between alar and basal plate
what are the roof plate and floor plate
Roof plate- dorsal midline end of developing spinal cord
Floor plate- ventral midline end of developing spinal cord
DO NOT contain neuroblasts, serve as pathway for nerve fibres to cross
describe the growth of spinal nerves
- motor nerve fibres appear in week 4
- they arise from nerve cell bodies which are present in the basal plate of the ventral horn
- Motor axons grow outside of the neuron in the basal plate
- the motor axon fibres collect into bundles forming ventral nerve root
- dorsal nerve root originates from nerve cell bodies in dorsal root ganglia positioned outside spinal cord.
- distal processes from dorsal and ventral horn join together to form spinal nerve
what do dorsal and ventral root fibres and spinal nerves carry
Dorsal root fibres- sensory innervation
Ventral root fibres- motor innervation
SPinal nerves contain BOTH sensory and motor fibres
when does brain development occur
week 3
what are the 3 primary brain vesicles that arise from the neural tube
o Forebrain – prosencephalon
o Midbrain – mesencephalon
o Hindbrain – rhombencephalonn
The 3 brain vesicles have ________ growth. This results in _______
Uneven
folds/ flexures
what are the flexures that are created due to uneven growth of primary brain vesicles
o Midbrain – cephalic flexure (head fold) – convex dorsally
o Pontine flexures – convex ventrally
o Cervical flexures at hindbrain/spinal cord junction, temporary (weeks 5-7), convex dorsally
convex dorsally
The 3 primary brain vesicles become a more complex 5 part brain. when does it occur and what is formed
week 5
Prosencephalon:
- Telencephalon
- Diencephalon
Mesencephalon
- Mesencephalon
Rhombencephalon
- Metencephalon
- Myelencephalon
what final brain structures does the prosencephalon form
Telencephalon forms:
- Cerebrum
Diencephalon forms:
- Eye cup
- Thalamus
- Hypothalamus and Epithalamus
- Mamillary bodies
what final brain structures does the mesencephalon form
Mesencephalon forms:
- midbrain
what final brain structures does the rhombencephalon form
Metencephalon
- Pons
- Cerebellum
Myelencephalon
- Medulla oblongata
what is spina bifida
failure or incomplete closure in posterior neuropore
what is anencephaly
failure or incomplete closure in anterior neuropore
how to prevent neural tube defects
folic acid taken prior to conception and in early stages of pregnancy reduces incidence
what is hydrocephalus
- Build up of CSF in the brain
- Hydrocephalus can INCREASE intracranial pressure on the brain cause damage
- associated with spina bifida
what is the treatment of hydrocephalus
Relieve intracranial pressure by shunting excess fluid into the abdomen via a surgically implanted shunt
what do the meninges develop from
Develops from mesenchymal cells and neural crest cells
when does development of the meninges happen and how
At day 25-30, mesenchymal and neural crest cells migrate around the neural tube
They form an
- external layer: dura mater
- internal layer (just from neural crest cells): pia mater and arachnoid mater
How is CSF made
made in brain ventricles
produced in choroid plexuses
how does build up of CSF causes problem in spina bifida cystica
CSF builds up in head in spina bifida cystics due to obstruction of the foramen magnum by the cerebellum
- > increased intracranial pressure
- > compresses brain
what does the developing eye appear as first and when does this happen
pair of shallow optic grooves
day 22
how are optic vesicles formed and when
the optic grooved form outgrowths from the diencephalon of the forebrain- now called optic vesicles
day 24
How are lens placode formed
Optic vesicles that are in contact with the surface ectoderm, they induce changes necessary for lens formation
–> lens placode (lens precursor) forms
lens placode cells become ______
columnar
Lens placode invaginate into ___________, forming the _________
optic vesicle optic cup (double walled)
how is the choroidal fissure formed
grooves arise on the ventral surface of the optic cup- forming the choroidal fissure
what passes along the choroidal fissure to supply the lens and developing retina
a branch of the opthalmic artery- HYALOID artery passes along the choroidal fissure to supply the lens and developing retina
optic cup is a ______ structure
bilaminar
Optic cup has two layers, what do these layers from
- Outer layer forms the pigmented layer of the retina
- Inner layer forms the nervous layer of the retina
what happens to the space between the 2 layers of the optic cup and how can this cause a problem
space disappears as axons grow from the optic nerve and fill that space up
since, there are two distinct layer, potential weakness remains e.g. detached retina after blow to the head
At the ____ of the optic cup, both layers of the retina give rise to the ____ and __________
rim
iris
ciliary body
_______ region of the optic cup forms the iris
marginal
what substance does the ciliary body produce and why is it important
aqueous humour
important in maintaining intra-ocular pressure in eyes + provides nutrients to ocular tissues
what is the lens derived from
surface ectoderm
Initally, lens is a _____ structure
hollow
what direction do the cells of the lens vesicle elongate and what do they form
cells of lens vesicle elongate anteriorly to form long lens fibres
do adult lens fibres contain organelles and why
NO
lens is transparent so no cellular material should be present
how is the transparent lens formed
the long lens fibres arrange in a laminar pattern to form a transparent lens
how does the optic nerve form
- optic cup connected to the brain by optic stalk
- the inner and outer layer of the optic stalk fuse and the cavity disappears.
- the inner layer cells of the optic stalk provide a network of neuroglia that support the optic nerve fibres
- optic stalk becomes optic nerve
what do the hyaloid artery and vein become
central artery and vein of the retina
how are the layers of the eyeball formed
the mesenchyme around the optic cup condenses to form the layers of the eyeball- the choroid and sclera
what happens to the most anterior part of the cornea
it becomes transparent- no blood vessels
how do the anterior and posterior chamber of the eye develop
- spaces develop in the mesencyme between the cornea and lens: anterior chamber
- fibrous tissue with a gelatinous substance fills the gap between the lens and retina: posterior chamber (vitreous body)
what are the molecular regulation involved in eye devolepment and where are they expressed
PAX6- key regulatory molecule
- expressed in anterior neural plate before neurulation begins
SHH- signalling molecule responsible for eye field separation
- SHH upregulates PAX2 in optic stalks and restricts PAX6 to the optic cup and lens
what are congenital cataracts
- lens opacity: can cause vision difficulties
- due to genetic causes or rubella infection between 4-7 weeks of gestation
what is microphtalmia
eye is too small
- due to genetic abnormalities, intrauterine infections, foetal alcohol syndrome
what is anophtalmia
absence of eye
- genetic/infection
what is cyclopia
single eye- failure of the prosencephalon to divide the orbits of the eye
very rare
can be due to mutations in SHH as it is responsible for separating the two field visions
Describe anencephaly
absence of major portion of brain skull + scalp
telencephalon structures fail to form -> cerebral hemisphers do not develop
infants do not survive after few mins of birth
