What does pseudostratified mean?
Despite the appearance of multiple layers, all the cells in pseudostratified epithelium are attached to the basement membrane, which is a thin layer of extracellular matrix.
Why is the early neuroepithelium pseudostratified?
- Due to migration of mitotically dividing nuclei- the cells aren’t moving around its their nuclei- giving the appearance of a multi-layered structure
(apical is on the inside due to the way the neural tube folded)
Where does each stage of division occur in relation to the polarity of the neuroepithelium?
- Nuclei move up in G1
- Nuclei move down in G2
- S phase is basal (outer membrane)
- M phase (division) occurs at the apical, ventricular surface
What do neuroepithelial cells divide asymmetrically to produce?
- Radial glia and neuronal precursors
Where does the neuronal precursor cell go?
- Migrates out into the mantel zone
(layer over the top) - Begin to differentiate at the upper layers
Happens in all CNS structures (same thing happened in the spinal cord)
How is Tritated thymidine used to track cell migration over time?
- Radioactive hydrogen put into thymine (Tritated thymidine) so it can be incorporated into newly synthesised DNA, a way of labelling
- Inject thymidine into mum rat- enters bloodstream of foetus
- Cells that are dividing take up the label so the cells that continue to divide will get less and less thymidine as each time the cells are dividing by half
- However, a cell that is born as a neuron on that day of early division i.e. stops dividing, will obtain the thymidine label - ‘label retaining cells’
Allows us to birth-date the cells allowing us to trace their migration to their final destination over time - Cells injected at different times/days, the later the days the further out the cells are
- NEURONS BORN AT DIFFERENT TIMES HAVE DIFFERENT FATES
How many layers of the neocortex are there and how can you see which TFs are in which?
6 layers
- If you label with different transcription factors you will see each of the layers has a characteristic set of TFs
What are heterochronic transplants and what do they show?
- Cells from an early embryo transplanted into an older embryo
- At the early stage the cells are ‘plastic’, they migrate and adapt to the cells being born at the same time in the host- end up at the upper layers
- Later born precursors when transplanted into a host migrate and adopt the fate that they would have had in the original cell due to the fact that they lose potency over time
What is lissencephaly?
- A mutation effecting migration which leads to the appearance of a ‘smooth brain’ with no sulci and gyri
- Majority of neurons found in the deepest layers due to dysfunction of neuronal migrations
- Also mutations in microtubule function (e.g. tubulin which pulls cells apart in cell division)
What are the boundaries of the cortical layers formed from the first migrations?
- The Cajal Retzius cells are the first migration from the ventricular zone
- The sub-plate neurons are below
These form the Pre-plate - Later migrating neurons form the cortical plate
How can Cajal Retzius cells be visualised?
Green Flourescent protein
How did Analysis of the RELN mouse mutant reveal what CR cells do?
- Mutation in reelin gene encoding large ECM protein expressed by CR cells
- Loss of reelin leads to failure of CR cells and subplate cells to separate and consequent disruption of layering cortex
- Thought to be because migrating neurons fail to stop
- Causes human lissencephaly
Why do Radial cell deplete over time?
- Progenitor cell numbers diminish and the mature cell numbers decrease
- More and more asymmetric division, later symmetric generative division
What are intermediate progenitors?
- Accumulate in the subventricular zone and continue to divide producing upper layer neurons
- Proliferation ceases in adulthood
What are Adult neural stem cells and where are they kept?
Subset of radial glial cells put aside to become astrocytes
The two major zones of adult SCs are:
1. Subventricular zone (olfactory bulb)
2. Dentate gyrus of hippocampus (spatial memory)
What are tangential migrations?
- The lateral movement of neurons
- Interneurons from the subpallium migrate through tangential migration to the forebrain
- These three interneurons are:
1. GABA-ergic inhibitory interneurons
2. Dopaminergic inhibitory
3. Cholinergic inhibitory
This is essential for diversity and the formation of brain structures
How is the cerebellum layered?
- Molecular cell layers (axons)
- Purkinje cell layer
- Granule cell layer (inner layer)
How does the granule cell layer form?
- In cerebellum the neural folds do not fuse, they give rise to the rhombic lips
- The anterior rhombic lip cells are migratory and proliferative
- They tangentially migrate to the external germinal layer on the hindbrain, eventually differentiating into granule neurons
- The granule neuron precursors go from this outside layer and radially migrate in leaving axons behind to form parallel fibres
What can mutations in RELN (the gene) do in addition to lissencephaly?
- Cerebellar hypoplasia
- Reelin (the protein) is expressed by granule neurons above and below the purkinje layer
- Mutations lead to disruptions in the cell layers of the cerebellum
- Reelin mutant mouse staggers around because cerebellum is centre for motor control
