mechanisms of neural development Flashcards
1
Q
How does the nervous system achieve its complex wiring?
A
- neurogenesis (creating right number of cells)
- migrations and differentiation (getting cells to the right place)
- axon guidance (growing an axon to the right target area)
- synaptogenesis (making connections with potentially useful partners)
- activity-dependent refinement (testing and perfecting the neural circuit)
2
Q
Neurulation
A
- inner surface is luminal surface, which eventually turns into the ventricles
- the outside becomes the outside of the brain - pial surface
- made of a single layer of neuroepithelial cells
3
Q
Neuroepithelial cells
A
- long thin cells - become radial glial cells later in development
- these are the progenitors for nerves and glial cells
- every so often they will release their hold on the pial surface, drop down to the luminal surface and will divide
- early on in development they divide perpendicular to the surface - daughter cells become neuroepithelial cells and part of the structure
- neural tube is gaining surface area, but so far we arent producing nerve cells
4
Q
Neuroepithelial cells to neurones and glia
A
- once the SA gets big enough, some will drop down but divide parallel to the surface
- these contain IC messengers and are polar - contact with the luminal surface means that they produce different messengers at this end
- if they divide perpendicularly they will always form neuroepithelial cells
- if they divide parallel, then the cell born furthers from the lumen will do something completely different - switch on different sets of genes and become neuroblasts
5
Q
Mutations in the control of neuroepithelial cell division affect brain size
A
- Mutation in microcephaly protein leads to the loss of microcephalin
- causes person to have a small head and brain with severe learning difficulties
- havent produced sufficient numbers of divisions and therefore nerve cells
- macrocephaly is also possible
- develops normally but doesnt have enough machinery inside
6
Q
Early development of the cerebral cortex
A
- neuroblasts reach up along process, grab onto the radial glial cells, pull themselves up and then repeat
- the nerve cells at first are very motile, they slowly crawl off onto the right place
7
Q
What do Morphogens do?
A
- all along the surface of the lumen cells are growing
- what cells these become, what genes these become, determining their future and behaviour - depends on morphogenic signals
- Bone morphogenic proteins are produced in the dorsal area
- SHH is produced ventrally
- there are gradients for morphogens stretching across the brain, medial to lateral, front to back
- these morphogens will switch on the right genes in order to get them to become the right cells and to migrate to the right place
8
Q
What are chemical guidance signals?
A
- tell the cells where they are supposed to go
- there are conc gradients for a variety of different guidance signals
- cells that are born at the cerebral cortex switch on genes, making them sensitive to Reelin - produced right on the pial surface, and so head straight to the top
- some born in the ganglionic eminence have genes switched on telling them that they are going to be an inhibitory neuron in the ccx - even though they are born so far away
- combination of genes switched on due to morphogens and guidance chemicals tell the cell where to go when migrating
9
Q
Neuroblasts migrate towards the pia mater
A
- Neuroblast climbs up to pial surface where it will take residence
- first cells to arrive are marginal zone cells
- the next ones come up and settle behind. These are called subplate cells
- The next wave move up and push through the subplate to be as close to the marginal zone as possible
- after this, each wave does the same thing, so the cortex is assembled inside out
10
Q
Cortical layers are created inside out
A
- as the waves of cells arrive, the morphogens are changing within the area that they are being born
- successive waves have different genes being switched on which will tell them to behave in different ways
- cells are being laid down in layers, with each successive layer having a different function
11
Q
What layers do what?
A
- first ones to arrive are deep layers (layers 5 and 6)
> excitatory ones are bid pyramidal cells that have long axons that go deep down to subcortical structures
> will project back down to thalamus and brainstem. (motor cortex they project down whole spinal cord as corticospinal tract) - middle layer (layer 4)
> turn into stellate cells
> receptive cells of the cortex - receive inputs from cortical areas such as thalamus - superficial layers (2 and 3)
> turn into small pyramidal cells that have projections to layer 4 in other cortical areas
12
Q
What other cells are produced?
A
- inhibitory interneurons are born in ganglionic eminence and migrate here
- once all the nerve cells you need have been produced, neuroepithelial cells start to produce glial cells
- astrocytes come from local neuroepithelial cells
- oligodendrocytes are produced in ganglionic eminence
- very complex pattern of migration
- when all are in place there are very few stem cells left
- subplate cells act to help direct the outgrowth and ingrowth of axons to the cortex
- about 4-6 weeks before both, marginal and subplate cells disappear - mature cortex
13
Q
Mutations affecting migration signals disrupt cortical organisation
A
- migration signals are essential
- reelin calls the cells below up to the cortical plate - if no reelin, cortex develops the wrong way round and it wont wire itself up correctly
- MRI shows that the cortex is way too thicl - not enough SA or infolding - gives severe learning difficulty and most likely epilepsy
14
Q
Axon guidance
A
- growth tips of neurites are called growth cones - actin filaments push membrane of filapodia out
- carry guidance signals
- depending on whether there are attractive guidance signals (actin bundles grow) or repulsive guidance signals (actin bundles shrink)
15
Q
Growth cones can swap receptor at specific locations
A
- axons don’t grow in a straight line, they will have to go through complex routes sometimes
- e.g. neuron in dorsal horn of spinal cord
- axon has to go around the lumen and up the contralateral side
- when it is developed, receptors are produced that mean that it is attracted towards the floor plate to go around the lumen
- when the axon touches the floor plate, the gene expression is altered and the attractive receptors are replaced with repulsive ones - causes axon to grow away from the floor plate, out laterally and turn up towards the brainstem
- they grow via a set of waypoints where they change expressed receptors and change direction
- some people lack receptors that cause the axon to go towards the floor plate and just grow straight up on the same side
