1. Development of CNS Flashcards
Describe the structure of the embryonic disc at 3 weeks (transverse section)
• 3 layers (inside => out)
- endoderm
- mesoderm
- ectoderm
• Neural plate - proliferation of ectoderm in dorsal midline
• Notochord - cartilaginous strip running through embryo (between endoderm and neural plate), in middle of mesoderm), ultimately forms the vertebral column
Describe the development of the embryonic disc
• As the neural plate thickens, it starts to fold up on the sides
• The 2 neural folds fuse dorsally (away from endoderm) to form a tube - neural canal
• Bunch of cells at tip of neural fold - neural crests
• Neural tube and neural crest are 2 independent sources of nervous tissue
- neural tube: all CNS cells
- neural crest: all PNS cells
• Neuroepithelium - wall of neural tube
Describe the 3 types of cells of the neuroepithelium
- Neuroblasts - all neurones with cell bodies in the CNS (include motor neurones)
- Glioblasts - become neuroglia (astrocytes and oligodendrocytes)
- Ependymal cells - line the ventricles and central canal (remain close to the inner membrane of the neural tube and spread out and form a lining around the developing ventricular system)
Where do microglia originate?
- Peripheral origin
* From systemic system => populate brain in early development
What are the 4 types of neural crest cells?
- Sensory neurones of dorsal root ganglia and cranial ganglia
- Postganglionic autonomic neurones
- Schwann cells
- Non-neuronal derivatives e.g. melanocytes
What is a common feature of neural crest derived cells?
Capable of migrating over quite large distances
Briefly describe the cross-section of the wall of the neural tube at an early stage
- Almost all cells attached to inner and outer membranes
- Nuclei of each cell in different positions
- Bigger cells near the inner membrane undergoing mitosis
Describe the differentiation of the neuroepithelium
• Cells withdrawing from the outer membrane => inner membrane (=> mitosis)
• One of the daughter cells stay attached to the inner cell membrane - gets bigger and goes into cell cycle again
• Other daughter cell migrates away and develops into neuroblasts
- develop processes (one becomes axon)
- axons are directed away from the inner membrane
• End up with 3 layers
- ependymal layer - by inner membrane (where mitosis occurs)
- grey matter - mainly cells bodies
- white matter - mainly axons
How is the differentiation of glioblasts and different to neuroblasts?
- Glioblasts can migrate into white matter as well
* Glioblasts do not develop axons (but do develop processes)
Describe the layers of the neural tube in cross-section
- Neural canal in centre
- Ependymal layer surrounds neural canal
- Roof plate (most dorsal part of canal)
- Floor plate (most ventral part of canal)
- Grey matter = mantle layer
- White matter = marginal layer
- Neural crests further out
What molecules control the whole process of differentiation and migration in the neural tube, and how?
- Signalling molecules, secreted from tissues around or cells within the neural tube
- Interact with receptors on the developing neuroblasts
- Guide the developing axons
- Can cause attraction or repulsion - direction determined by concentration gradient (higher conc. closer to signalling molecules)
- Timing is important - some signalling molecules have different effects at different stages of development, neurones need to have the right receptors
How does the neural canal and grey matter change at a later stage of development?
• Neural canal is even smaller compared to the thickness of the wall
• Grey matter splits into 2 different types:
- Alar plate - dorsal - sensory
- Basal plate - ventral - motor
What information do the interneurons in the alar plate receive?
- Sensory information
* From developing dorsal root ganglia (developed from neural crest)
Where does information from the basal plate go?
- Motor function
- Interneurons and developing motor neurones
- Therefore, axons leave spinal cord here, to go towards muscles
How is the white matter of the spinal cord split in later development?
- It isn’t dorsal/ventral
* It is mixed
Describe the cross-section of a mature spinal cord
- (neural canal is now) Central canal carrying CSF
- (Alar plate is now) Dorsal horns
- (Basal plate is now) Ventral horns
- Dorsal root joins dorsal root ganglion
- Ventral root joins further down
- Whole spinal cord (horns and canal) is surrounded by thick layer of white matter
Describe the gradient of molecules around the notochord and how this effects cells in the neural tube
• Several signalling molecules produced by notochord
• Concentration gradient established
• Highest concentration near notochord
• Cells closest to molecules induced to become motor neurones
(• Molecules produced by ectoderm, dorsally, inhibit differentiation into motor neurones)
Describe the development of the brainstem
- Firstly, development of 4th ventricle
- Roof plate (dorsal/posterior) starts proliferating rapidly and dorsal part of brainstem exapnds laterally
- Roof plate pushes alar plates aside from dorsal to lateral to the roof plate
- Cranial nerve nuclei with motor function tend to lie more medially - where the basal plates are
- Sensory - lateral
- Autonomic - in between
What are the three primary vesicles that the wall of the anterior neural tube differentiates into - at around 4 weeks (which will develop into the brain)?
- Prosencephalon - future forebrain
- Mesencephalon - future midbrain
- Rhombencephalon - future hindbrain
Following the 4th week, how do the vesicles divide in the formation of the brain?
- Prosencephalon (most anterior) => telencephalon + diencephalon
- Mesencephalon doesn’t divide
- Rhombencephalon => pons + medulla
- Therefore, 5 secondary vesicles present at 5 weeks
What happens to the developing forebrain following the 5th week?
- Expansion of telencephalon (top/anterior part)
- Develops into cerebral hemispheres (cerebral cortex)
- Less expansion in lower part
- Diencephalon - thalamus and hypothalamus
What happens in the developing brain around 8 weeks?
- Growth of wall of neural tube
- Space within becomes smaller => ventricular system
- 3rd ventricle forms in diencephalon (forebrain)
- Aqueduct becomes narrow (midbrain) - drains into 4th ventricle (hindbrain)
- First development of cerebellum - from the back of the pons
When looking at a lateral view of the developing brain at 4 weeks, what are the flexures called, starting anteriorly?
- Cephalic flexure
- Pontine flexure
- Cervical flexure
Describe the proliferation and migration of neuroblasts in the wall of the developing hemisphere of the brain
• Proliferate near inner membrane
• Some stay in the middle to form the basal ganglia
• Others migrate towards the outer membrane
- attach to radial glial cells (like scaffolding)
- cell bodies anchored in inner membrane and have a single long process to the outer membrane
• Wave of proliferation near inner membrane then wave of migration to outer surface forming one layer of cortex
• Waves continue until you have six layers within cerebral cortex
• 1st layer - acellular, local connectivity layer to neurones below
• Layers 2-6 - lamina of neurones, functional connections in fully developed brain
• Each layer has different types of cells with different functions/connections
In which trimester/weeks of pregnancy does the majority of brain development take place?
1st trimester - first 12 weeks
What can disrupt brain development during pregnancy
• Genetic and environmental abnormalities:
- mother’s lifestyle
- diet (folate and vit B12)
- teratogens (agent that disrupts development of embryo)
What neural tube deficit can a deficiency of folic acid lead to?
Spina bifida
What does rostral and caudal mean?
- Rostral - towards head
* Causal - towards spinal cord
Give 2 examples of rostral neural tube deficits
- Anencephaly - lack of brain
* Encephalocele - herniation of brain through the unfused skull (ectopic brain substance - out of skull)
Give 4 examples of causal neural tube deficits
- Spina bifida - lack of closure of chordal part of tube (may not be visible externally)
- Dysraphism - lipoma formed, large fatty deposit
- Meningocele - meninges herniate
- Myelomeningocele - spinal cord herniates
