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23 Cards in this Set
- Front
- Back
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MAIN MIGRATORY ROUTES |
CORTEX projection neurons that are made in a ventricular/subventricular zone. Move radially up. Intn made in ventral part of brain. In ganglionic eminences. Move tangentially up to cortex. Cerebellum both tangential and radial. Pons - tangential migration |
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DIFFERENT NEURONAL TYPES MIGRATE FROM DISTINCT ORIGINS |
Cajal-Retzius cells important for migration of projection neurons. They are made in 3 different locations - cortical hem, antihem, ant. neural ridge. Migrate tangentially over brain surface. |
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MIGRATION OF CAJAL-RETZIUS CELLS |
Meninges needed for hem-derived CR cells by providing physical substrate and signalling. Ephrin mediated contact repulsion leads to homogeneous distribution over brain surface. Contact inhibition of locomotion (cells change direction of migration upon contact with another cell) |
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MIGRATION OF CORTICAL INTN |
Made ventrally in ganglionic eminences. Attractive and repulsive cues that guide their migration Attractants in cortex, repellants in striatum (sema) Intn have branched leading process. They sense envt and look for cues |
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PROJECTION NEURONS |
Migrate radially. |
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DLN AND ULN |
Projection neurons to deep layers and polarise. The leading process will contact the marginal zone. It stabilises and cell pulls itself up along with nucleus. SOMAL TRANSLOCATION |
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DLN AND ULN II |
Cortex much thicker later on. After multipolar phase and extension of leading process, won't reach marginal zone immediately. Processes from RG used as scaffold. Attach and migrate until close enough to MZ to stabilise. |
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ZONES IN DEVELOPING CORTEX |
Marginal zone Cortical plate Intm zone Subventricular zone Ventricular zone |
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PHASES OF RADIAL CORTICAL MIGRATION |
Start as multipolar. Travel to intm zone where they transition to BP shape. In early borne finish migration w/ somal translocation. Later borne need glia-guided locomotion b4 terminal translocation. |
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MULTIPOLAR MIGRATION AND MP TO BP TRANSITION |
Intm zone dense with axons. Become MP to navigate through it. Axonal extension to sense envt. Proneural genes are upregulated (may explain morphology) Two types of migration : sep and rep |
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MUTANT PHENOTYPES FOR MP-BP TRANSITION |
Mutant Filamin A - impairs migration in multipolar phase LIS1 RNAi - arrest neurons in multipolar phase too. Can't transition to BP FILIP RNAi - targets MFA migration normally. Premature bipolar (excess Filamin A) DCX RNAI - produce doublecortin. Cant transition DCX Over express - excess bipolar cells where they shouldn't be |
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CDK5 FOR NEURONAL POLARISATION AND CORRECT LAMINATION |
/KO stuck in MP phase. Transition doesn't happen. Disorganised cortex. /p35, p39 important for function Cortical plate and prelate structure disrupted. Subplate ectopic (superficial) |
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CDK5 phos. several protein in migration |
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PHASES OF LOCOMOTING STAGE |
Adhesions keep neurons in touch w/glial process - tight apposition (cad) not enough = weak - cant pull nucleus up Leading process extends Swelling in front of the nucleus Centrosome moves into swelling Nucleus follows centrosome Leading process extends |
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CYTOSKELETON |
Actin - actomyosin contractility in leading process Block actomyosin activity stops nuclear movement MT- LIS1 and Dynein needed for nucleokinesis /migration |
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DCX, sun1/2 and syne1/2 |
Attach membrane of nucleus to MT. Interfere with function of cells move nucleus up. |
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MOLECULAR PATHWAYS INV IN LOCOMOTING STAGE |
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SOMAL/TERMINAL TRANSLOCATION |
Reach MZ. Contain RG endfeet, cajal retzius cells and migrating intn. ECM attachment and DUAL SIGNALLING FROM CR cells: Secreted protein - reelin Cell adhesion protein - nectin Dab1 |
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REELIN |
Limk1- factin stability Phos - inhibit severing activity Akt -neuronal adhesive properties GSK 3B - phos serine9 to inhibit activity (active site availability) Rap1- control Cadherin func to regulate somal translocation Mutations to target dab1 effectors |
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RAP1 |
Needed for somal translocation. KO affects migration of neurons to cortical plate. Cell adhesion reg. via Cadherin and integrins. Cadherin - stabilise leading process Integrins - anchor glial endfoot at cortical MZ |
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NECTINS LINK RAP1 AND CADHERINS IN REELIN PATHWAY |
Nectin 1-3 mediate interaction between CR cells and (leading process) - critical for radial migration Cdh2 recruitment inhibited upon afadin KO in neurons Nectin 3 recruit afadin/Rap1 complex to regulate Cdh2 via p120ctn |
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NECTINS LINK... |
CR cells express adhesion mol. Nectin1 Neocortical projection neurons express nectin 3 Reelin increases p120ctn recruitment to afadin. P120 and Cdh2 glia independent St. |
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SUMMARY OF MOL. PATHWAYS INV IN RADIAL CORTICAL MIGRATION |
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