Neuronal migration 1,2,3 16.11 Flashcards
Wher are the vast majority of neurons born?
Ventricular zone
What are the main migratory routes in the developing brain for different neurons?
(2 marks)
- Projection neurons: generated in ventricular zone migrate radially up
- Interneurons: generated in ventral part of brain in ganglionic emminences - move tangentially up to cortex
What kind of migration is present in the cerebellum and pons?
In both cerebelleum AND pons: transgential mirgation
Cerebellum only: radial migration
Where are cajal restzius cells produced?
(2 marks)
In cortical hem, antihem, and anterior neural ridge, migrate transgentially over brain surface and cover completely
How does the pre-plate lead to the formation of cajal retzius cells in the marginal zone?
(3 marks)
- @ v early stages of development have pre-plate on top of ventricular zone
- Pre-plate has future subplate neurons and cajal retzius cells
- 1st neurons that migrate split up into cajal retzius cells in marginal zone and sub-plate neurons at the bottom
What are meninges?
Membranes that protect the brain
Outline the migration of cajal retzius cells.
(4 marks)
- Move on surface of brain where meninges located
- Meninges provide physical substrate and CXC42/ CXCR4 signalling - restricts movement of CR cells to most superficial part of marginal zone
- Eph/ ephrin - mediated contact repulsion mediates homogenous distribution over the brain
- Due to ^^ don’t get areas with high cell count or completely devoid of cells
How does migration happen in cortical interneurons?
(4 marks)
- Attractants in cortex
- Repellents in striatum form of Sema 3A/3F
- Migrate through leading, sense environment and look for cues
- Centrosome and nucleus move in an established branch
Pic: orange - area of high concentration of attractants, so branch nearest to it move towards it and other one is retracted. Have movement of interneuron to where centrosome and nucleus move into established branch
How do projection neurons migrate?
- Radially
What experimental methods can be carried out to view the migration of projection neurons?
(6 marks)
- In utero: use electroporation
- Apply electrical currents to palsmid DNA
- Progenitors will take up plasmid and express what’s in it and neurons will take it up
- Gets diluted as no more plasmid because given to neurons
- Can put on specific promoter
- After few days can see migration of plasmid
- Band at E18 is missing, then know something gone wrong
What is the first type of neuron generated in the deep layers?
Projection neurons
By the time the first deep layer neurons are generated, what is the cortex looking like?
(2 marks)
NO CORTEX
- Cortical wall very thin
What is somal translocation?
(2 marks)
- When cells go through multipolar pahse and because cortex thin, leading process contacts marginal zone
- Once contacted, stabilise there - cell will put itself up, moving nucleus up
How does glial giuded translocation occur?
(3 mark)
- Use process from RG cells as they act as a scaffold
- Attatch to process and migrate along process until close enough to marginal zone
- Leading process can stabilise itself and established itself quiety
What do neurons use as a basis for glia guided locomotion?
Radial glial processes as a scaffold to move up
What are the phases of the locomoting stage?
(3 marks)
- Swelling formed, in leading process of ahead nucleus and centrosome moves into swelling
- Nucleus the follows and moves into swelling
- Leading process extends further forming new swelling
- Repeat
What are the molecular pathways involved in the phases of locomoting stage?
What do adhesions do?
(2 marks)
- Cadherins mediate attatchment between neuronal processes and RG fibres
- Cadherins i.e. CDH2, CDH4 - cooperate to regulate migration in mouse brain by protein tyrosine phosphotase 1B.
What can be seen in a dominant negative mutant of CDH?
(3 marks)
- Neurons stuck in the intermediate zone and intefere with normal CDH function
- multipolar neurons aren’t stuck as their neurons formed a leading process that’s properly oreintated to the CP, but nuclei remain in IZ
- Neurons have ‘wavey’ processes and much less associated with RG processes
What group of GTPaeses regulate cadherin levels at the surface of migrating neurons?
RabGTPases