Lecture 12 (6) - Mechanisms of Axonal Pathfinding Flashcards Preview

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1

Attractive signal

microfilaments and microtubules accumulate at the contact site

2

Growth cone at tip

webby
• different regions, filopodia stabilized by actin
--> growth cone to attractive

3

Mechanisms of axonal pathfinding

• stereotropism
• haptotaxis
• chemotropism

4

Stereotropism

physical barriers
• axons move around physical objects
• some artificial substrates
• repair tissues/nerves

5

Haptotaxis

movement along substrate bound molecules
• most common
• bound to cell surface

* molecules of the extracellular matrix and cell surface molecules
* selective fasciculation of axons : labelled pathways hypothesis

6

Chemotropism

diffusabe factors

7

1. Stereotropism - physical barriers

• collagen fibers
• plastic barrier
• artificial substrate
• tunnel

8

2. Haptotaxis - movement of growth cones along substrate bound molecules

ECM: glycoproteins and proteoglycans

9

Cell adhesion proteins control

mobility and guide toward movement
• cell-cell adhesion
• cell-matrix adhesion

10

Cell-cell adhesion

• classical cadherins (E, N, P, VE), homophilic binding, associated with cytoskeleton (actin filaments) via catenins
• Ig family members (N-CAM, ICAM), homo- and heterophilic binding

11

Cell-matrix adhesion

• Integrins (many types), heterophilic binding associated with cytoskeletion (actin filaments), via talin, paxillin, filamin, etc.
• transmembrane proteoglycans (syndecans), heterophilic binding

12

To find molecules that axons like, use

cell culture assays

13

Cell culture as guidance molecules - assays are used for identifying
1. cell-adhesion assay

• can the neuron stick to other cells or a given substrate

14

Cell culture assays for identifying guidance
2. stripe assay

• petri dish - different areas with different molecules
• neuron in, where its axon grows =
which stripe is attractive or repulsive

15

Haptotaxis I - ECM-molecules facilitate or inhibit axonal growth

CSPG - chondroitin-sulfatproteoglycan
• dorsal roof plate of spinal cord
• when growth cone reaches CSPG, is repulsed and turns away

laminin attracts

16

Haptotaxis II - cell adhesion molecules are involved in axonal outgrowth, fasciculation and pathfinding

most growth cones grow on the surface of other axons or cells
• only if 2 molecules recognize each other
• floor plate instructs axons to grow along (cross midline) or repulses
• the midline is transient in embryos

17

Midline - axons express

axonin1 on surface

18

Cells of the floor plate have

NRCAm - both adhesions and bind to each other
• axon guided to cross midline

19

Incubate floor plate with

antibodies = 1 or 2 can't pass
• antibodies block sites where 1 or other cross = can't bind

20

3. Selective fasciculation

the "labeled pathways" hypothesis
• guidance on axon
• G - neurons grow where nothing else arond axon
• recognizes molecules on axon P
• grows to decision point and sees P missing
--> stalls
= absence of whole axon tracks

21

Fasciculation is affected in

fasciclin II mutant flies
• FasII is expressed on pioneer axons of longitudinal tract

22

4. Chemotropism

guidance by diffusable factors
• repulsive factors lead to growth cone collapse
• collapsin = growth cone turns away and collapses
• growth cone collapses, grows, tries again

23

Collapsin

growth cone turns away and collapses
• collapses, grows, tries again

24

Pathfinding of the DRG-axons is based on

repulsive factors
• spinal cord
• DRG cells grow straight bc repulsed by secreted substance

25

4. Chemotropism

• NGF - nerve growth facctor
• all axons like NGF
• follows this diffusible factor

26

Both in vertebrates and invertebrates the CNS midline plays an important role in

organizing the axonal scaffold
• vertebrates - floor plate = epithelial cells, transient
• in embryo, guides axons in midline (attracts/repulses)
• cross = turn ant/post

27

Commissural

crosses ventral midline

28

Ipsilateral

doesn't cross ventral midline

29

Netrin is expressed in the

CNS midline of Drosophila
• CNS midline - explant of growth plate to Dci
• Dci attracted to plate over distance
--> shows diffusible factor (later called netrin)

30

Netrin exists in

vertebrates and invertebrates