How to make a brain - development of CNS Flashcards
What does the CNS develop from?
The CNS develops from a tiny patch of neural plate (ectoderm)
What factor regulates growth within development to stop us from being all nervous system?
We would be all nervous system if it wasn’t for BNP which makes skin etc, BNP is inhibited during nervous system growth
Mention how early development occurs and what it looks like up to day 19?
In early development we have a neural plate which has columnar epithelium (neurectoderm) on its surface and sits above the notochord.
The plate will make a tube which is called neurulation and around day 19+ a midline groove becomes apparent. Neurulation is induced by the bar shaped tissue - notochord (deep to neural epithelium)
How does development look around days 20-21 (third week)?
On days 20-21 the cells on the plate edge thickens forming folds and a groove referred to as the neural fold and groove (looks like a trench dug out in middle). Somites start to form in the midline of the edges of the tube.
What happens around the fourth week?
Contractile actin at apex of each cell, constricts and makes apex smaller, bases stay same and get curvature
Cells on edges of folds start to sense each other and throw out projections so they touch and adhere and this starts to form the neural tube
The starts initially in the cervical region
This process is called neruilation ( ormation of tube from plate)
What occurs around day 25 and day 27?
Closure of the neural tube occurs at the rostral end at day 25 and you have a rostral neuropore formed
And the caudal end of the tube closes on day 27 creating the caudal neuropore
What happens if the neuropores fail to close?
Anencephaly (a type of neural tube defect - NTD)
Failure of neural tube to close - rostral neuropore. Causes;
- Infants to be born without a forebrain
- Usually unreactive to light and sound
- Usually stillborn
- Some infants may exhibit aspiration and respond to touch and sound if brainstem is intact.
0.5 - 1 peer 1000 live births
What are the risk factors for developing a neural tube deficiency and what do we do to prevent it?
Risk factors for neural tube deficiency;
- folate deficiency
- Previous anencephaly
- diabetes
- epilepsy drugs
Its now a policy in UK if thinking of becoming pregnant supplement diet with folate
What are the different types of defects in caudal neuropore?
These are all types of Spina bifida - clinically significant in 1/1000 births
- Spina bifida occulta - normal apart from hair on surface
- Meningocele - bulges but spinal cord is in spinal column
- Meningomyelocele - spinal cord protrudes
- Myeloschisis - most severe! neural tissue on arch of back
- Myeloschisis - when neuropore doesn’t close and we have folded neural tissue outside
What is a disease marker that is used to check from neural tube defects?
Alpha fetoprotein (AFP)
- its also used for some cancers and liver diseases as well
How does the neural tube form the brain?
3 swellings develop got become the brain;
- Prosensecephalon (becoming forebrain)
- Mesencephalon (becoming midbrain)
- Rhombencephalon (Hindbrain)
These vesicles keep connected throughout life and spinal cord is attached. This space has CSF and is continuous
How does the forebrain, midbrain and hindbrain develop?
Forebrain;
- Grows two lateral expansions connected to a central slit like space
Mid brain;
- Grows slower than forebrain and remains as a single central tube
Hindbrain;
- Develops into (rest of the) brain stem and cerebellum with a central ventricle expanding
How does the lumen of the tubes develop ?
Forebrain;
- Forms two lateral ventricles and a third ventricle (with thalamus around it)
Midbrain;
- Forms a cerebral aqueduct
Hindbrain;
- Forms fourth ventricle
How do the walls of the tube develop in the forebrain?
The telencephalon (end brain) containing the cerebral hemispheres
Diencephalon grows containing the thalamus and hypothalamus
How do the walls of the tube develop in the hindbrain?
The Midbrain (mesencephalon)
Hindbrain (Rhombencephalon) grows 2 parts;
the metencephalon containing Pons and cerebellum
the myelencephalon containing the medulla
Why do the cerebral hemispheres grow in a curve and how does this explain the shape of the internal structures?
The forebrain vesicle becomes the cerebral hemispheres.
At week 6 the cephalic flexure starts to grow.
Around 12 weeks there is strong relative growth of the temporal lobes and they have outgrown their space so grows a bit like a boxers glove, growing downwards and forwards making a C-shape. This also grows around the developing insulation hence why it becomes an island surrounded by temporal, parietal and frontal lobes.
If you remember C shape of lateral ventricles this will help
What happens around 16 weeks to the shapes of our cerebral hemisphere?
The cerebral hemisphere is c-shaped, can see central sulcus and lateral fissure with insula buried.
The brain has a more crinkled surface which is more gyro to increase surface and volume of grey matter
How does the curved growth affect the shape of the internal structures of the brain?
The following structures are curved;
The corps callosum - a huge hemisphere connection
The fornix (important for memory (connects hippocampus with anterior structures) - growth of temporal lobes creates looping in fornix
Hippocampus (memory function) due to fornix getting longer thee hippocampus descends into the temporal lobe
Lateral ventricle
Interventricular foramen - fluid filled space
How can we see these c-shapes in the adult brain?
Can see c-shaped corpus callosumn, how 3rd ventricle loops, the fornix
What forms our c-shaped internal grey matter?
Basal ganglia - contains caudal nucleus which follows shape of lateral ventricle
How is Basal ganglia split?
Its split by ascending and descending white matter bundle - the internal capsule
It splits apart the caudate nucleus and the lentiform nucleus (which contains putamen + globus pallid us)
What components form the basal ganglia and draw how they are arranged?
Putamen is part of the lentiforrm nucleus which also includes globes pallidus hidden within it. It looks like a big stone in the middle.
The caudate nucleus attaches to this and wraps itself around the putamen in a c-shape.
The internal capsule is located around the middle at the superior end of the caudate nucleus and the thalamus is located more medial-inferiorly to the putamen.
The amygdala is NOT a basal ganglia structure but is at the end pf the caudate nucleus.
There is also substantial nigra and sub thalamus that are part of basal ganglia but elsewhere
How does the fourth ventricle form?
Around week 6 the poutine flexure appears and widening of the roof of the fourth ventricle occurs.
What happens to the sensory grey matter before and after the back of the brain stem is opened out?
Sensory grey matter is in dorsal position before the 4th ventricle forms
After the 4th ventricle forms the sensory grey matter tends to be more lateral
How does the cerebellum develop?
The cerebellum develops in the dorsal wall of the neural tube.
How does the brain stem look once development has occurred?
Grey matter in brain stem is dorsal rather than ventral
There is a superior and inferior colliculus in the midbrain
The floor of the 4th ventricle is in the pons
There is fasiculus cuneatus and fasiculus gracillis in the medulla
What side do the 12 cranial nerves exit ?
They exit ventrally as the grey matte is at the back of the brainstem so cranial nerves come out front
What does the caudal neural tube develop into?
The caudal neural tube becomes the spinal cord.
The caudal neural tube has three layers which will undergo cell division to make;
- Ventricle layer - which will make progenitor cells, neurons/glia for the mantle layer
- Mantle layer - will make neuron bodies/glia
- Marginal layered processes of neuron build here (white matter conc on outside)
What are regions called as the spinal cord develops?
Sulcus limitans - sulcus in middle
Alar lamina (posterior basal lamina) - becomes sensory (somatic/visceral)
basal lamina (anterior basal lamina) - becomes - motor somatic/visceral
How does the connections to the PNS grow?
Ingrowth of neurites from the dorsal root ganglion cells (DRG) forms dorsal root
Outward growth from neurons motor grey forms ventral root
What induces the neural tube formation and nerve cell specialisation?
We would be all nervous system if it wasn’t for BNP - Bone morphogenetic protein which inhibits neural ectoderm, promoting skin
Noggin, chordin, follistatin produced in the notochord block BMP - allows default differentiation of neural ectoderm
What happens neural test cells ?
Neural crest undergo a transition and instead of being stuck there they then become migratory and spread through embryo giving arise to a wide range of tissues
Neural crest cells give rise to so Manny cells but what are the main ones in the CNS that they give rise to and why is it important we know these?
- Cranial nerve ganglia
- Autonomic ganglia
- Schwann cells
- Craniofacial skeleton
- Melanocytes
This is important as a defect in neural crest cell can be fatal to a developing embryo as they make so many key things
Name 2 neural crest development disorders ?
Waardnburg’s syndrome (autosomal dominant 1/50,000)
- Some types have Pax-3 gene deletion which controls some aspects of neural crest
- Pigment abnormalities (even albinism) (1 lock of hair white like cruel de vill)
- Deafness
- Constipation
- Heterochomia of eyes
- Telecanthus - widen spaces of eyes
Treacher Collins Syndrome (autosomal dominant 1/50,000)
- Defective protein called Treacle (TCOF1 gene)
- Failure of formation/apoptosis of neural crest cells
- Abnormal eye shape
- Micrognathia
- Conductive hearing loss
- Underdeveloped zygoma
- Malformed ears
- Craniofacial skeleton developed incorrectly
