Mechanisms of Cell Migration Flashcards
What are the two types of radial migration and what do they involve?
Radial migration - along radial glia - perpendicular to ventricular surface
Tangential migration - orthogonal to radial glia - parallel to ventricular surface
Describe the process of projection neuron migration in the cortex
Originate from cortical precursors
Migrate radially through cortex
Describe the process of interneuron migration in the cortex
Originate from subcortical regions - lateral ganglionic eminence (LGE) and medial ganglionic eminence (MGE)
Migrate tangentially through cortex - radially to correct position in cortical plate
What is the leading process of a neuron and what does it consist of?
Lamellipodium
Meshwork of actin, filipodia of actin bundles, microtubules
Adhesion complexes at leading end
Describe the process of somal translocation
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
What controls nuclear movement?
Autonomous mechanisms - e.g. Lis1, Nudel, Dynein, Dcx, Dclk
What is the effect of a Lis1 mutation?
Lissencephaly - abnormally smooth brain lacking organised layers
What is the purpose of Lis1?
Binds microtubules - promotes stability
Forms complex with Dynein and Nudel - required for centrosome-nucleus coupling and regulation of nuclear transportation
What is the effect of a Lis1 KO using RNAi?
Neurons stop in SVZ
What is the purpose of Dcx and Dclk?
Microtubule-associated - promote polymerisation and stabilisation - regulate nucleokinesis
What is the effect of a Dcx KO using RNAi?
Neurons stop in IZ
What is Reelin?
Extracellular matrix protein - secreted in marginal zone of cortex
Describe the effect of Reelin
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
What are Reeler mice?
Reelin mutation
Layering defects of cortex - inverted lamination
What is the process of cortical interneuron migration?
Tangential from subpallidum to cortex - branched leading process
Radial later - take position in cortical plate
What are the two initial streams of migration within cortex?
Marginal zone
Subventricular zone
Later some neurons cross cortical plate - change streams
What are the signalling molecules involved in the guidance of cortical interneurons?
Chemoattractive signals in cortex
Chemorepulsive signals in subpallidum
Describe the process of cell-to-cell signalling in cortical interneuron migration
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
What is the effect of Cxcr4 mutant mice?
Interneurons move into cortical plate early - improper distribution - disrupts lamination
