DEVELOPMENT OF CEREBRUM AND CEREBELLAR CORTICES

Question 1

What types of migration are there?

Answer 1

Radial

Tangential

Question 2

The neuroepithelium is one cell thick but appears as many layer due to what?

Answer 2

Their pseudostratified nature.

Question 3

What is interkinetic nuclear migration?

Answer 3

It is the movement of the cell nucleus of the neurepithelia as they undergo progression throught the cell cycle.

Question 4

Mature neurons accumulate over time in the layers above the ventricular zone by radially migrating. This is occurring in all CNS structures and is important for the what?

Answer 4

The layers of the CNS

Question 5

How do we know that mature neurons accumulate in the layers above the ventricular zone?

Answer 5

Use of birth dating to follow neurogenesis and migration.

Question 6

How is birth dating carried out?

Answer 6

Tritiated thymidine incorporates into newly synthesised DNA and inject into pregnant females. The labelled DNA incorporates into cells in S phase, however only those in their final division retain over time. Cells born early (ie early injection) will occupy the lower layers of the cerebral cortex. By bith dating we can trace migration to the final destination.

Question 7

The first born neurons occupy the deepest layers of the cortex whereas the latest born occupy what?

Answer 7

The most superficial layers.

Question 8

Cortical neuronal fates change over time. What happens in an early precursor is transplanted into an old host embryo.

Answer 8

Since the early precursors are still plastic they take on the fate of the cells being born at the same time as the host.

Question 9

What happens in later born precursors if they are transplanted into an younger host?

Answer 9

Their fates have become fixed over time so instead migrate to adopt the fate of the position they would have if they had not been transplanted.

Question 10

What does failure in migration cause?

Answer 10

Lissencephaly, loss of gyri and sulci from the layers of the brain and neurons have failed to migrated and are found in the deeper layers.

Question 11

What mutations are associated with licessephaly?

Answer 11

Usually mutations in proteins associated with microtubules as they are critical for migration
TUBA1A, TUBB2B, LIS1, DCX

Question 12

Earliest post mitotic cells migrating form the ventricular zone form what? And what kinds of cells is this made from?

Answer 12

They form the pre-plate, made up of Cajal Retzius cells in the marginal zone and the subplate neurons below.

Question 13

Later migrating neurons after the pre plate has been set up form the cortical plate, in which major layers of the cortex from. Where do these sit?

Answer 13

They use cells as a scaffold to migrate upwards to sit beween the Sub plate and Cajal cells which are now called the marginal and intermediate zone. (Sub plate neurons later die.) This layer will from the cortical plate in which the major layers of the cortex will form.

Question 14

What do we know of Cajal Retzius Cells?

Answer 14

Discovered by Cajal and Retzius - 1890
First post mitotic cells to appear
Characteristic morphology
Can visualise with GFP

Question 15

What is the Reeler mouse and what does it reveal?

Answer 15

The Reeler mouse is a mutant that revealed what Cajal cells do.
Loss of Reelin (an ECM protein expressed by Cajal cells) leads to failure of subplate cells and Cajal cells to separate and therefore loss of organisation in the layers of the cortex. It is thought that Cajal cells normally tell migrating neurons when to stop.

Question 16

What can Reelin mutations cause?

Answer 16

Lissencepahly

Question 17

Radial glia become depleted over time, hoever what happens to the intermediate progenitors?

Answer 17

Intermediate progenitors accumulate in the subventricular zone and continue producing upper layer neurons. This will occur until adulthood.

Question 18

What are the zones of the cortex?

Answer 18

Ventricular
Subventricular
Intermediate 
Subplate
Cortical Plate
Mantle

Question 19

Although radial glia become depleted over time, what happens to a sub-set of radial glia?

Answer 19

They become astrocyte like and are put aside to become adult neural stem cells that can produce new neurons.

These can be found in the subventricular zone of the 4th ventricle and in the dentate gyrus of the hippocampus.

Question 20

How does Tangential Migration occur?

Answer 20

If radial migration were all that occurred, the pattern of TFs and cell fates induced in the neuroepithelium would persist in the neurons of the mantle zone (the most superficial layer). Some key neuronal sub-populations must migrate to and from other regions.
Eg. Major classes of neurons source in the subpallium and migrate.
1. GABA-ergic inhibitory interneurons
2. Dopaminergic inhibitory interneurons
3. Cholinergic inhibitory interneurons

Question 21

What is unusual about the migrations in the cerebellar cortex?

Answer 21

The cortex of the cerebellum is also layered however tangential migration occurs first and then radial migration. This also occurs from the most superficial layer to the deepest layer.

Question 22

What are the layers of the cerebellar cortex?

Answer 22

Molecular layer
Purkinje cell layer
Granule layer

Question 23

How do major cerebellar neuronal types get derived?

Answer 23

Neural folds of the hind brain remain unclosed and give rise to rhombic lip cells (the hind brain equivalent of neural crest cells). Anteriorly, daughters migrate tangentially to form the external germinal layer to become granule neurons.
Posteriorly daughters migrate tangentially to become the potine nuclei and inferior olive of the ventral hindbrain.

Question 24

What are factors conrolling cerebellar development?

Answer 24

1. ATOH1 (atonal like transcription factor) - KO = hypoplasia
2. Sonic hedgehog released from purkinje cells increase levels of lobulation and causes medulloblastoma
3. Reelin - KO = cerebellar hypoplasia and ataxia