HNN Topic 16 - Development of the CNS Flashcards
How is SHH involved in eye development?
- Needed for forebrain development - separates L and R side
- Early in eye development needed to separate the eye field to give two eyes
- Also has role in creating optic stalk (with PAX 2/6)
What is the result of disruption of migration of neural crest cells?
- Treacher-Collins Syndrome
- Under development of zygote bone and ears
- Mutation of TCOF1 gene, retinoic acid exposure?
- Di George Syndrome
- 22q11.2 deletion syndrome
- Cleft palate, cardiac abnormalities, abnormal facies, thymic aplasia
Describe the structure of the brain during week 5 of developement
- Prosencephalon - telencephalon + diencephalon
- Telecephalon - cerebrum
- Diencephalon - eye cup + thalamus, hypothalamus + epithalamus
- Mesencephalon - midbrain
- Rhombencephalon - metencephalon + myelecephalon
- Metencephalon - pons + cerebellum
- Myelencephalon - medulla oblongata
From where do neural crest cells originate?
- Tissue at top of neural folds becomes pinched off - neural crest tissue
- Neural crest cells at lateral border dissociate, change from epithelial to mesenchymal
- Leave neuroectoderm by active migration and displace, enter underlying mesoderm
What is the first step in development of the neural tube?
Development of the notochord
- Tube extends from primitive streak in opposite direction
- Tube first forms axial process, then notochord process, then notochord
What causes congenital cataracts?
Genetic causes, rubella infection between 4-7 weeks
What is the inductory function of the optic vesicles?
In contact with the surface ectoderm, induce changes necessary for lens formation
How do neural tube defects occur?
- Result of failure of/incomplete closure of neural tube
- Anterior neuropore - anencephaly
- Posterior neuropore - spina bifida
- Most common in lumbosacral region
What is the inductive role of the notochord?
Notochord induces overlying ectoderm to thicken and form the neural plate
What forms the iris and ciliary body?
At rim of optic cup, both retinal layers form iris and ciliary body
Describe the structure of the brain at week 3 of development
- 3 primary brain vesicles
- Forebrain - presencephalon
- Midbrain - mesencephalon
- Hindbrain - rhombencephalon
- Uneven growth produces folds/flexures
- Midbrain - cephalic flexure, head fold, convex dorsally
- Pontine flexure - convex laterally
- Cervical flexure at hindbrain/spinal cord junction, temporary (5-7 weeks), convex dorsally
Describe the growth of spinal nerves
- Motor axons from basal plate (ventral horn) - week 4
- Neurons in dorsal root ganglia extend towards dorsal horn and periphery
- Dorsal root fibres carry sensory innervation, ventral root fibres carry motor
- Spinal nerves - sensory + motor
When does the developing eye first appear?
At 22 days as pair of shallow grooves - outgrowths of the diencephalon called optic vesicles
List the genes resposible for molecular regulation of eye development
- PAX 2/6
- Sonic hedgehog
When do the cerebral hemispheres divide?
Week 8
When does the developing CNS first appear? What is the first sign of its development?
Appears at week 3, first sign = thickening of ectoderm in primitive streak
What are the consequences of myelomeningocoele spina bifida?
- Nerves at level of lesion are damaged/don’t form properly
- Loss of sensation/paralysis below level of defect
- More cranial = more serious
Describe the closure of the neural tube
- Begins in cervical region, moves cephalic and caudally
- Open ends form anterior and posterior neuropores - connect with overlying amniotic cavity
- Closure in week 4 - anterior neuropore by day 25, posterior by day 27
Describe the folding of the neural plate
- Lengthens and lateral edges elevate (neural folds), midline depresses (neural groove)
- Folds join at midline - forms neural tube
Describe the formation of the eyelids
- Folds of ectoderm with mesenchyme between that grow over the cornea
- Fuse, enclosing a conjunctiva/sack anterior to cornea
- Inner layer of ectoderm becomes conjunctiva, fuses with cornea
- Lacrimal glands form as ectodermal buds from the upper conjunctival sac into the surrounding mesoderm
- Eyelids separate again between 5th and &th months in utero
Describe the types of spina bifida
- Occulta - mild, tuft of hair in skin over defect
- Meningocoele - meninges protrude though gap in vertebrae, least common
- Myelomeningocoele - flattened, plate-like mass of nervous tissue with no overlying protective layer
Where does the sulcus limitans extend to?
Mesencephalon
Define gastrulation
Process by which 3 germ layers are formed - ectoderm, mesoderm, endoderm
Describe the formation of the lens
- Initially hollow, derived from surface ectoderm
- Cells of lens vesicle elongate anteriorly to form long lens fibres - adult fibres contrain no organelles or nuclei
- Arrange in a laminar pattern to form a transparent lens
What is the initial event in neuralation?
Cells of neural plate make up neuroectoderm
Describe the shape of the neural tube
Wider at cranial end, narrower at caudal end
List types of eye abnormalities
- Congenital cataracts
- Microphthalmia
- Anophthalmia
- Aniridia
- Cylopia
What is microphthalmia and what causes it?
Eye too small, genetic abnormalities/intrauterine infections/foetal alcohol syndrome
From where does the choroid plexus develop?
Develops where pia mater and ependyma come into direct contact e.g. roof of fourth ventricle
Describe the formation of the optic nerve
- Optic cup connected to brain by optic stalk hyaloid vessels in choroidal fissure
- Inner and outer layer fuse. Cavity of stalk disappears. Inner layer cells provide a network of neuroglia that support the optic nerve fibres
- Optic stalk forms optic nerve. Hyaloid artery and vein become central artery and vein of the retina.
Describe the formation of the structure of the spinal cord
- Longitudinal groove = sulcus limitans, divides dorsal and ventral horns
- Roof plate (dorsal) and floor plate (ventral)
- No neuroblasts
- Pathways for nerve fibres to cross from one side to the other
- Eventually can see
- Dorsal, ventral and intermediate horns (sympathetic portion of ANS neurons, only in thoracic and upper lumbar segments)
- Ventral fissure, dorsal median septum
How can neural tube defects be prevented?
Folic acid prior to conception and in early stages of pregnancy reduces risk
Describe the path of neural crest cells
- Cells from trunk go through holes in basal ganglia, form melanocytes + hair follicles
- Also go to dorsal root ganglion etc - migrate ventrally though anterior somite
- Migrate from cranial end before neural tube has fully closed - contribute to craniofacial skeleton + neurons for cranial ganglia, glia and melanocytes
Which germ layer is the notochord derived from?
Mesoderm
Describe the signalling which occurs to regulate neuralation
- Up-regulation of FGF, inhibition of BMP-4 causes induction of neural plate
- Chordin and noggin help inhibition of BMP-4
- Neural plate switches from E-cadherin to N-cadherin expression
Describe the structure of the optic cup
- Bilaminar structure
- Outer layer forms pigmented layer of retina
- Inner layer forms nervous layer of retina
- Space between layers disappears as axons grow from optic nerve
- Potential weakness remains - detached retina after blow to head
How do the neural plate cells change during neuralation?
Become more columnar
When is development of the eye complete?
Week 10
Which tissues are derived from ectoderm?
CNS, PNS, sensory epithelium of ear/nose/eye, epidermis, hair + nails, subcutaneous, mammary/pituitary gland, enamel of teeth
What is the difference between E-cadherin and N-cadherin?
E is epithelial, N is mesenchymal (migratory - prevents fusion of neural tube and ectoderm)
How does the structure of the lens begin?
- Starts as placode, cells become columnar + invaginate, pushes against optic vesicle
- ‘Double-walled cups’
How is PAX 6 involved in development of the eye?
- Key regulatory molecule
- Expressed in anterior neural plate before neuralation begins
- Correct expression required to control inductive events that form the lens and cornea
Describe the differentiation of the spinal cord
- Neuroepithelial cells (thick pseudostratified epithelium) extend over entire neural tube, give rise to neuroblasts
- Neuroblasts form mantle layer - later forms grey matter
- Outer marginal layer contains nerve fibres emerging from neuroblasts in the mantle layer - becomes myelinated white matter
- Thickening of dorsal and ventral aspects
- Dorsal - alar plate (sensory)
- Ventral - basal plate (motor)
What determines the folding of the neural plate?
Depends on a number of factors:
- Intrinsic factors - cytoskeleton, stage of cell cycle
- Extrinsic factors - adhesion points e.g. within notochord, surface ectoderm
What are the meninges derived from?
- Mesenchymal and neural crest cells
- Day 20-35, cells migrate from around neural tube, form external layer (dura mater) and internal layer (pia and arachnoid mater)
What is anophthalmia and what causes it?
Absence of eye - genetic/infection
Describe the development of the eyeball
- Mesenchyme around optic cup condenses to form layers of eyeball - choroid and sclera
- Anterior cornea becomes transparent
- Spaces develop in mesenchyme between cornea + lens - anterior chamber
- Fibrous tissue with a gelatinous substance (vitreous humour) fills the gap between the lens and retina - vitreous body, posterior chamber
What is aniridia and what causes it?
Absence of iris, mutation in PAX 6
Describe the blood supply to the developing eye
- Grooves arise on ventral surface of the optic cup forming the choroidal fissure
- Branch of ophthalmic artery (hyaloid artery) - passes along the choroidal fissure to supply the lens and developing retina
What is cylopia and what causes it?
Single eye, failure of prosencephalon to divide orbits or eye - mutation in SHH gene
What is a common complication of spina bifida?
Hydrocephalus:
- Especially in spina bifida cystica
- CSF builds up due to obstruction of the foramen magnum by the cerebellum
- Large head
- Raised ICP - compression of brain
- Drain fluid into abdomen using shunt to relieve pressure
What do neural crest cells give rise to?
Ganglia, Schwann cells, adrenal medulla, melanocytes, connective tissue in head
