478-485. Development of the CNS Flashcards
Which germ layer do the meninges arise from?
Mesoderm
What cells are the anterior meninges derived from?
Neural crest cells
Where are the meningeal layers of the trunk and caudal head regions derived from embryologically?
Paraxial mesoderm
Which layer develops first and on what day of development?
Pia mater; day 24
Around what day of development is the dura mater first seen?
Day 45
Around what day is the arachnoid mater first seen?
Day 57
What secretes CSF and where is CSF secreted into?
Choroid plexus; brain ventricles
Fills the subarachnoid space and the ventricular system around and inside the spinal cord and brain
Fills ventricles, cisterns, sulci, and central canal of spinal cord
How much CSF is produced a day?
How much CSF is circulating at any one time?
400-500ml
125-150ml (as it’s constantly being reabsorbed)
What is the role of CSF?
Fluid “floats” brain providing cushioning and bouyancy so that it’s weight does not compress the cranial nerves on the inside of the skull
Describe the general structure of the choroid plexus
Sac like invaginations which project into the ventricular cavity
What are ependymal cells? What type of epithelium are they?
A type of glial cell which lines the ventricular cavities and the central canal of the spinal cord - the epithelium like lining of the brain
Ciliated simple columnar shape
Are ependymal cells involved in the production of cerebrospinal fluid?
Yes
What does the myelencephalon go on to become in the developed brain?
Medulla oblongata
What does the roof plate of the myelencephalon consist of?
A single layer of ependymal cells covered by pia mater
What is a Chiari malformation?
When the cerebellum pushes down into the spinal level and obstructs the foramen magnum
What symptoms are associated with a type I Chiari malformation?
Headache Neck pain Balance issues Dizziness Difficulty in swallowing
What conditions are mainly associated with type II Chiari malformations?
Individuals with hydrocephalus, spina bifida cystica, syringomyelia (CSF filled cyst within the spinal cord)
What defect causes type I Chiari malformation?
Defect in mesoderm
What defect causes type II-III Chiari malformation?
Defect in neuroectoderm
At what time do the alar and basal plates form in spinal cord development?
Week 5
When do the alar and basal plates differentiate into the dorsal and ventral horns?
Week 7-8
Which plate forms the dorsal horn and which plate forms the ventral horn?
Dorsal horn - alar plate
Ventral horn - basal plate
Where and how do the primary brain vesicles form?
Arise from the neural tube
Once tube has formed and closed, the anterior portion expands quicker than the posterior forming the primary brain vesicles which differentiate into secondary brain vesicles
The remainder of the neural tube becomes the spinal cord
What first stimulates the formation of the neural plate?
The appearance of the notochord which induces thickening of the ectoderm
What do the cells of the neural plate make up?
The neuroectoderm
What is the neural tube derived from?
Ectoderm
What is the embryological origin of the notochord?
Mesoderm (lies beneath ectoderm)
What is the first stage of neurulation?
Neural plate lengthens and start to edges elevate (depressed mid-region forms neural groove)
When the neural folds (of neural plate) start to increase in height, what does the neural groove become?
Median hinge point (cells here remain attached to notochord
Which hinge point(s) allow the lateral edges of the neural plate to meet one another, forming the neural tube?
Dorsolateral hinge points (DHPs become wedge shaped to bring neural folds together)
What is the tissue around the neural tube?
Mesoderm - paraxial, intermediate, lateral plate
What induces neural tube formation?
The up regulation of FGF, which inhibits BMP-4
over-expression of BMPs prevents neural tube formation
What 3 things inhibit BMP-4 expression?
FGF, chordin and noggin
Why does the neural plate switch from E-cadherin to N-cadherin expression?
Allows two ends of neural folds to recognise each other and fuse
Prevents fusion of newly formed neural tube to overlying ectoderm
What are neural crest cells?
Tissue at the top of the neural folds which is pinched off and leaves neuroectoderm by active migration and displacement (highly migratory)
What are the derivatives of neural crest cells?
Ganglia Sympathetic neurons Schwann cells Adrenal medulla Melanocytes and hair follicles Connective tissue in head region
Contributes to craniofacial skeleton as it migrates from cranial end of embryo before its closure
What malformations can be caused by disruption of neural crest cell migration?
Treacher Collins syndrome (under development of zygomatic bones and ears - mutation in TCOF-1 gene/retinoic acid exposure)
Di George Syndrome (cleft palate, cardiac abnormalities, abnormal facies, thymic aplasia - 22q11.2 deletion)
What are the opening ends of the neural tube called?
Anterior and posterior neuropores
When does closure of the neuropores take place?
Week 4; anterior closes d25, posterior closes d27
What type of epithelium are neuroepithelial cells?
Thick pseudo-stratified epithelium which give rise to neuroblasts
What are the histological features of neuroblasts? What are they?
Large round nuclei, pale nucleoplasm, dark stained nucleoli - primitive nerve cells
What do neuroblasts give rise to?
The mantle layer, which later forms the grey matter of the spinal cord
What is the marginal layer made of, and what does it give rise to?
Made of nerve fibres emerging from neuroblasts in the mantle layer
Becomes white matter of spinal cord by myelination of nerve fibres
What forms the
a) ventral horn - motor area of spinal cord
b) dorsal horn - sensory area of spinal cord
a) basal plate
b) alar plate
Where are the intermediate horns of the spinal cord present and what neurones do they contain?
Thoracic and upper lumbar regions; sympathetic neurones of the ANS
Describe the development of the spinal nerves
Motor axons extend out from the basal plate
Dorsal root ganglia extend towards the dorsal horn and periphery
Dorsal root fibres - sensory information
Ventral fibres - motor information
Spinal nerves contain both sensory and motor neurones
What are the 3 primary brain vesicles and when do they form?
Forebrain - prosencephalon
Midbrain - mesencephalon
HIndbrain - rhombencephalon
Week 3
Where is the cephalic flexure located?
Midbrain - convex dorsally
Describe the pontine flexure
Convex ventrally
Where is the temporary cervical flexure?
At junction of hindbrain and spinal cord - convex dorsally (weeks 5-7)
What are the 5 brain ventricles and when do they appear?
Week 5
Prosencephalon - telencephalon and diencephalon
Mesencephalon
Rhombencephalon - metencephalon and myelencephalon
What is formed by the telencephalon?
Cerebral hemispheres
What is formed by the diencephalon?
Thalamus, hypothalamus, epithalamus and infundibulum
What is formed by the mesencephalon?
Same- midbrain - motor control, hearing, vision
What is formed by the metencephalon?
Cerebellum and pons
What is formed by the myelencephalon?
Medulla oblongata
What is caused by failure of the anterior neuropore’s closure?
Anencephaly
What is caused by failure of the posterior neuropore’s closure?
Spina bifida (most common in lumbosacral region)
Describe spina bifida occulta
Mildest form
No protrusion of spinal cord
small tuft of skin over skin where defect lies
Describe meningocoele
Spina bifida where there is normal vertebrae but meninges bulge through gaps
Describe myelomeningocoele
Spina bifida with whole involved area of lesion
No overlying protective membranes
Associated nerves at area of lesion damaged or not formed - can cause loss of function or paralysis
The higher up, the more severe
Describe hydrocephalus and its features
Water on the brain Associated with spina bifida Large head shape A cerebral anomaly Raised pressure
What is anencephaly
Absence of major portion of the brain, skull and scalp - incompatible with life
Normally failure of telencephalon structures
What do the meninges arise from?
Mesenchymal and neural crest cells
When does development of the meninges take place?
Between days 20-35
What causes the build up of CSF in spina bifida cystica?
Obstruction of the foramen magnum by the cerebellum - raised pressure and compression of brain
How is hydrocephalus treated?
Shunting of fluid
What are lens fibres?
Long thin transparent cells which lie underneath the epithelium
They have a high protein content - crystallins
When does the eye begin to develop?
Day 22 - as a pair of shallow grooves
What are the optic vesicles?
Outgrowths of the diencephalon of the forebrain (arise from the grooves)
Optic vesicles are in contact with surface ectoderm and induce changes necessary for lens formation
What cells become more columnar and invaginating as the optical vesicles develop further?
Lens placodes
What is the blood supply of the developing eye?
HYALOID ARTERY (a branch of the opthalmic artery) This supplies the lens and developing retina
Runs through the choroidal fissure (formed by the grooves which arise on the ventral surface of the optic cup)
The optic cup is a bilaminated structure. What is formed from the:
a) outer layer
b) inner layer
a) Pigmented layer of the retina
b) Nervous layer of the retina (forms rods and cones)
What causes the space between the two layers of the optic cup to disappear?
Axons growing from the optic nerve
What weakness remains with relation to the eye after development?
Detached retina after blow to the head
What does the rim of the optic cup give rise to?
Iris and ciliary bodies
Where is the lens derived from and how is it arranged during development?
Arises from surface ectoderm
Lens is initially hollow
Cells of lens vesicle elongate anteriorly to form long lens fibres (in adults there are no organelles or nuclei)
Arrange in a laminar pattern to form a transparent lens
What is the role of PAX6
A key regulatory molecule present in the anterior neural plate before neurulation begins
What is the role of SHH with relation to the development of the eye?
Signalling molecule responsible for eye field separation
Upregulates PAX-2 in optic stalks and restricts PAX-6 to the optic cup and lens
List 4 congenital eye abnormalities
Congenital cataracts
Cyclopia
Microphtalmia
Anophtalmia
What causes congenital cataracts?
Genetic causes
Rubella infection between 4-7 weeks gestation
What is microphtalmia and what causes it?
Eyes are too small; genetic abnormalities / intrauterine infections / foetal alcohol syndrome
What is anophtalmia and what causes it?
Absence of eye - genetic cause/infection
What is cyclopia and what causes it?
Single eye - failure of the prosencephalon to divide the orbits of the eye
Mutations in SHH
