Mechanisms of Cell Migration

Question 1

What are the two types of radial migration and what do they involve?

Answer 1

Radial migration - along radial glia - perpendicular to ventricular surface
Tangential migration - orthogonal to radial glia - parallel to ventricular surface

Question 2

Describe the process of projection neuron migration in the cortex

Answer 2

Originate from cortical precursors

Migrate radially through cortex

Question 3

Describe the process of interneuron migration in the cortex

Answer 3

Originate from subcortical regions - lateral ganglionic eminence (LGE) and medial ganglionic eminence (MGE)
Migrate tangentially through cortex - radially to correct position in cortical plate

Question 4

What is the leading process of a neuron and what does it consist of?

Answer 4

Lamellipodium
Meshwork of actin, filipodia of actin bundles, microtubules
Adhesion complexes at leading end

Question 5

Describe the process of somal translocation

Answer 5

Cytoplasmic swelling in leading process - proximal to nucleus
Centrosome linked to nucleus by cage of microtubules - moves into swelling
Nucleokinesis - nucleus pulled towards centrosome by dyneins associated with microtubules - actomyosin contraction drives nucleus forward

Question 6

What controls nuclear movement?

Answer 6

Autonomous mechanisms - e.g. Lis1, Nudel, Dynein, Dcx, Dclk

Question 7

What is the effect of a Lis1 mutation?

Answer 7

Lissencephaly - abnormally smooth brain lacking organised layers

Question 8

What is the purpose of Lis1?

Answer 8

Binds microtubules - promotes stability

Forms complex with Dynein and Nudel - required for centrosome-nucleus coupling and regulation of nuclear transportation

Question 9

What is the effect of a Lis1 KO using RNAi?

Answer 9

Neurons stop in SVZ

Question 10

What is the purpose of Dcx and Dclk?

Answer 10

Microtubule-associated - promote polymerisation and stabilisation - regulate nucleokinesis

Question 11

What is the effect of a Dcx KO using RNAi?

Answer 11

Neurons stop in IZ

Question 12

What is Reelin?

Answer 12

Extracellular matrix protein - secreted in marginal zone of cortex

Question 13

Describe the effect of Reelin

Answer 13

Binds to VLDLR and ApoER2 receptors - activates SFKs - phosphorylate intracellular adaptor protein Dab1 - activates downstream targets - regulates microtubules - causes neurons to stop in appropriate layers

Question 14

What are Reeler mice?

Answer 14

Reelin mutation

Layering defects of cortex - inverted lamination

Question 15

What is the process of cortical interneuron migration?

Answer 15

Tangential from subpallidum to cortex - branched leading process
Radial later - take position in cortical plate

Question 16

What are the two initial streams of migration within cortex?

Answer 16

Marginal zone
Subventricular zone
Later some neurons cross cortical plate - change streams

Question 17

What are the signalling molecules involved in the guidance of cortical interneurons?

Answer 17

Chemoattractive signals in cortex

Chemorepulsive signals in subpallidum

Question 18

Describe the process of cell-to-cell signalling in cortical interneuron migration

Answer 18

Cxcl12 chemokine secreted by meninges and immediate precursors in IZ/SVZ - binds to Cxcr4 and Cxcr7 receptors on migrating interneurons
Cxcl12 distribution guides interneurons in 2 streams - MZ and IV/SVZ

Question 19

What is the effect of Cxcr4 mutant mice?

Answer 19

Interneurons move into cortical plate early - improper distribution - disrupts lamination