NEURODEVELOPMENT AND NEUROREGENERATION Flashcards
Which layer does neural tissue develop from?
The ectoderm (top layer of the embryo)
What is the ectoderm responsible for giving rise to?
- Neural tissue, skin, hair
Where about in the ectoderm do the cells become nueral tissue?
- Middle region of the ectoderm
What is neurulation?
- The formation of the neural tube from the neural plate rolling up into a tube
What is the centre of the nerual tube filled with?
- Lumen (centre of tube) is filled with fluid (CSF comes from here)
Where does the CSF derive from?
Lumen of neural tube
What occurs if the neural tube doesn’t close?
Spinobiphida as it is exposed to the external environment
Where does the neural tube first join up?
- First joins up in the middle, then zippers up to closure points.
What is neurogenesis?
- When progenitor cells proliferate to become neuroblasts
Where do cells divide?
- Divide with the nucleus at the ventricular surface
How to neuroblasts divide?
Assymetrically
Why is nueroblasts division assymetric?
- To retain a pool of progenitor cells (APCs)
- Initially one cell thick but must form multiple layers
Where are the newer cells found?
Further out to surface of brain
What are the migrating cells controlled by?
- Cells that produce factors that tells cells when to stop migrating.
What do parts of the neural tube swell to become?
- Vesicles that form different parts of the brain
What do the growth factors control?
- The transcription factors
How are cells differentiated into different cell types?
- Soluble growth factors are released from regions and affect cells around them by altering transcription factors ..so cells around them interact differently
How do pyramidal neurons in cortex synapse on motor neurons in the spinal cord?
- Needs stimuli such as touch and smell (soluble things in body to guide neurons down spinal cord)
How do neurons find their target?
They extend a growth cone at end of axon
What (in genera) controls axon guidance?
Environmental signals
e.g. attraction/repulsion, guidance cues
What can attractive and repulsive signals cause respectively?
- Attractive directs actin fibres to extend by encouraging polymerisation and repulsive signals cause actin filaments to retract (depolymerise)
What are dividing cells called?
- Neural progenitors (progenitor cell)
What are radial glial cells?
- Neural progenitors that give rise to all neurons and astrocytes of CEREBRAL CORTEX (most neurons of CNS)
How do we give rise to billions of neurons in the brain?
- Symmetrical division to expand population of progenitors (both daughter cells remain in VZ)
- Assymetrical division occurs later in development
What occurs in assymetrical divison?
- Daughter cell migrates away to set position in cortex where it will NEVER DIVIDE AGAIN
- Other daughter cell stays in VZ to undergo more divisions
- Radial glial cells repeat pattern until all neurons and glia of cortex have been generated.
What is the fate of the migrating daughter cell determined by?
- Age of the precursor cell
- Position within VZ
- Environment at the time of division
How do daughter cells migrate?
- (neural precursor cells) follow path from VZ toward surface of brain
- Migrate along thin fibres emitted by radial glial cells
When do radial glia withdraw processes?
- Radial glia withdraw processes when migration is complete.
What does the architecture of cortical dendrites depend on?
INTERcellular signals
What 3 phases do differentiation of neurons differ in?
- Pathway selection
- Target selection (what to innervate)
- Address selection (correct layer of LGN for example)
- neurons extend the axons as they differentiate
What are the different ways cells communicate ( in differentiation) ?
- Cell-cell contact
- Contact b/w cells and extracellular secretions of other cells
- Communication between cells over a distance with diffusable chemcials
When does a neuron differentiate?
- Once the neural precursor cell has migrated to take up its appropriate place in the NS
- After this, THEN IT EXTENDS PROCESSES (will eventually become axon and dendrite)
What is the growing tip of the neurite called?
- GROWTH CONE!
What does the growth cone contain on the inside?
Actin filaments and mitochondira and microtubules
What does the growth cone do?
- Identifies an appropriate PATH for neurite elongation (recognises it)
What is an important substrate for axonal growth?
- Extracellular matrix (growth only occurs if the matrix contains certain proteins)
What is the extracellular matrix?
- fibrous proteins deposited in spaces between cells
Which interaction promotes axonal elongation?
- Integrins (surface molecules that growing axons express) that bind LAMININ (glycoprotein)
What is fasciculation ?
- CAMs (cell adhesion molecules) are expressed
- Causes axons growing together to STICK TOGETHER ( so the axons grow in unison)
What are pioneer axons?
- “stretch” as the nervous system expands and they guide developing neighbour axons to the same targets
How do pioneer axons grow in the correct direction?
- Axon trajectory (pathway) broken into segments (few 100 microns long)
- Finishes segment when it arrives at an intermediate target
- Like connecting the dots
What determines whether guidance cues are attractive or repusive?
- Receptor expressed by the axons
What is a chemoattractant?
- Diffusable molecule that acts over a distance to attract growing axons to their targets (to form spinothalmic tract e.g.)
Why don’t our CNS axons regenerate?
- If axon is cut in CNS, severed tip initially forms growth cone but then aborted
- Due to ‘nogo’ which is molecule released when oligodendria are damaged- inhibits regeneration
What happens if a CNS alpha motor neuron axon is cut in the PERIPHERI?
- Grows back to its target (because severed IN Peripheri)
What is the detailed process of synapse formation?
- Growth cone approaches muscle fibre
- Agrin released to cause Ach to gather beneath the axon
- Neurotransmitters vesicles enter axon terminal
- Extracellular matric produced (connects neuron to muscle cell)
- Neurtrophin (survival factor) determines which axon remains at synapse
What is a more general process of synapse formation (lecture) ?
- Make contact
- Contact stabilisation (cell-cell interaction)
- Synaptic maturation: recruit synaptic machinery to site of immature synapse
- neural activity regulates synaptic connections
What do the pyramidal neurons extend?
- Apical dendrite and multiple basal dendrites
- length increases postnatally
What occurs to dendritic spines in some neurodevelopmental disorders?
- Spine shape is altered (or not quite right)
Do the number of synapses increase or decrease with age?
- DECREASE! (peak at 5yrs)
- Synapses are eliminated that aren’t required
When do electrophysiological properties develop?
- Early in the embryo but undergo significant changes in maturation (production of ion channels changes response)
- Important in axon guidance
What can development in brain be influenced by?
- Genes and environmental factors both pre and postnatally
Where do astrocytes and oligodendrocytes (CNS) develop from?
- The neural plate
- Important in synaptogenesis
When does gliogenesis begin?
After neurogenesis has finished
Where do microglia develop from?
- The immune system
What is used to try and study human brain development without killing animals and what is the process?
- Growing human organoids
1. human embryonic stem cells isolated
2. Then grow them in certain ways and expose to certain factors
3. This forms mini brain like strucutres
What range of cell types to brain organoids contain?
- Vesicles
- Neural retinal tissue
- Neuroepithelial cells
What are 2 examples of immunofluorescent markers?
- SOX2 - neuroepithelial marker
- TUJ1- labelling differentiated neurons
What are the advantages of organoids?
- Different regions of the brain can be made
- Different neural cell types
- So good for studying evolution of the brain
- good for looking at patient mutations (pluripotent stem cells- can grow into organoid and compare to normal patient)
- Look at Glioma (cancer development in brain)
What are the disadvantages of organoids?
- NO good way of having blood cells supply organ in dish
- can only vasuclarise them by putting them in mouse brain
- Microglia (immune system) only come in AFTER vascularisation of brain
What type of models used for Zika virus?
Mouse
What type of models used for Austism
Also mouse models