development of the cortex

Question 1

what are the three stages to cortex development?

Answer 1

proliferation, migration and differentiation

Question 2

what is the pial surface?

Answer 2

the outermost layer of the neural tube

Question 3

what is the ventricular surface?

Answer 3

the innermost layer of the neural tube

Question 4

proliferation/DNA replication in cortical sheets

Answer 4

interkinetic nuclear migration
nucleus of neuroblast (neural stem cell) moves up and down the radial axis of the cortical sheet (from ventricular surface to the pial surface), synchronising with the progression of the cell cycle
they divide and form daughter cells

Question 5

what are the two main TF that control gene expression?

Answer 5

notch-1 (apical surface) and numb (basal surface)

Question 6

vertical cleavage of notch-1 and numb

Answer 6

equal distribution of notch-1 and numb in the north and south poles respectively

Question 7

horizontal cleavage of notch-1 and numb

Answer 7

only one cell has notch-1 and the other has numb (different to original parent cell)

Question 8

what process does just notch-1 evoke?

Answer 8

migration

Question 9

what process does just numb evoke?

Answer 9

continues proliferation

Question 10

radial migration

Answer 10

radial glia bodies in the ventricular zone send long processes up to the pial zone, forming a scaffolding for progentitor cells to migrate along radial glial fibres

Question 11

inside-out cortical layer development

Answer 11

neurons are generated in the ventricular zone (VZ)
these neurons then migrate outward to the cortical plate (CP)
the first neurons to be born migrate the shortest distance and settle in the deepest layers of the cortex (layers V and VI)
subsequent waves of neurons, born later, migrate past these early-born neurons to form more superficial layers (layers IV, III, II, and I)

Question 12

stellate cells

Answer 12

interneurons that migrate to the granular layer (layer IV) and are involved in local cortical circuits, primarily providing inhibition

Question 13

pyramidal cells

Answer 13

excitatory projection neurons that migrate to more superficial layers (layers III, V) and contribute to long-range signaling in the brain

Question 14

what does Gde2 do?

Answer 14

inhibits notch

Question 15

what happens if a mouse has no Gde2?

Answer 15

it will have lots of notch therefore fewer cells migrate to start with
this means there are fewer cells in initial layers (V and IV)
however as there has been more proliferation there are lots of cells in II and III=overexpression

Question 16

what causes outside-in cortical development?

Answer 16

a reelin/reeler mutant

Question 17

what is reelin?

Answer 17

a secreted glycoprotein from cajal-retzius cells at the pial layer

Question 18

what can also cause reeler mutants?

Answer 18

mutations to receptor transduction pathways in radial glia and migrating neurons

Question 19

how does reelin deficiency cause outside in development?

Answer 19

normally, reelin signals to neurons through the reelin receptors to halt their migration (detatch from radial glial fibres) at the correct cortical location
without reelin, neurons fail to stop migrating at their proper layer and instead continue moving toward the pial surface, eventually forming incorrect cortical layers
this defect leads to an outside-in pattern in which newer-born neurons end up in deeper layers, and the older-born neurons accumulate at the cortical surface
cells can no longer migrate through previous layers

Question 20

what is the result of reelin deficiency?

Answer 20

reelin mutants can exhibit a condition called lissencephaly which refers to the lack of a normal, folded cortical surface
this results in impaired neuronal networks and defective cortical function
the disorganized layering leads to faulty connections between neurons, impairing sensory processing, motor control, and higher cognitive functions

Question 21

what are the problems with the detach and stop hypothesis of reelin?

Answer 21

local reelin release doesn’t stop migration
neurons that dont respond to reelin dont end up in higher coritcal layers

Question 22

what is the detach and go hypothesis?

Answer 22

the “detach and go” model helps explain how neurons can progressively move through the developing cortex in a stepwise fashion without losing direction or getting stuck. this process ensures that neurons can migrate long distances from their birthplace in the ventricular zone to their final positions in the cortical plate, while maintaining their correct orientation relative to the radial glial fibers by detaaching from the glial fibre and reattaching to a fibre closer to the glial surface