Axon Guidance

Front 1

growth cone fan shaped sheet

Back 1

lamellipodia

Front 2

path of spinal commisural axons?

Back 2

extend toward the ventral most region of the spinal cord and cross the floor plate to the contralateral side and then extend rostrally

Front 3

four classes of guidance cues known to instruct commissural axons during development

Back 3

repellents from the dorsal spinal cord; attractive cues from the ventral spinal cord; repulsive cues in the ventral spinal cord facilitating midline crossing and preventing re crossing;and attractants that guide post-crossing commissural axons anteriorly toward targets in the brain

Front 4

example of strict molecular identification of axon targets

Back 4

retinotectal connectivity results in inverted projection on the tectum of the visual world

Hint 4

topographic maps in the retinotectal system: nasal (anterior) retinal axons project to posterior tectum and vice versa

Front 5

netrin receptors

Back 5

include members of the DCC and UNC5 family

Front 6

semaphorins

Back 6

5 secreted and others are transmembrane or GPI-linked proteins; receptors include plexins and neuropilins

Front 7

Netrin protein as an axon attractant

Back 7

floor plates secrete netrins and in the spinal cord a dorsal-to-ventral increasing gradient of netrin-1 protein can be found `

Hint 7

this gradient guides commissural axons to the floor plate; this attractive effect is mediated by DCC family receptors

Front 8

Netrin repulsive actions

Back 8

require receptors of the UNC5 family

Front 9

netrin bifunctionality depends upon..

Back 9

receptor composition and intracellular signaling; neurons that express DCC on their surface respond to Netrin-1 as an attractant. if neurons express both DCC and UNC5 receptors then these form a signaling complex which now interprets Netrin1 as a repellent

Hint 9

inhibition of cAMP-mediated signaling using a PKA inhibitor converts Netrin1 attraction to repulsion even though these neurons only express DCC

Front 10

semaphorins are potent repellents

Back 10

expressed in tissues surrounding many peripheral nervs and acts as a repellent for sensory and motor axons

Hint 10

can provide surround repulsion: drive axon-axon fasciculation

Front 11

Sema3a can act as both an attractant and a repellent

Back 11

for distinct neural processes extending from mouse cortical pyramidal neurons

Front 12

what converts Sema3a from repulsion to attraction

Back 12

cGMP stimulation

Front 13

Slit

Back 13

midline repellent allow commissural axons to cross the CNS midline and not remain stuck at the midline owing to netrin attraction

Front 14

guidance at the midline step 1: initial attraction/repuslion

Back 14

netrin1 and SHH at the floor plate act as attractants

Hint 14

BMP signaling at the dorsal midline function as repellents that serve as a push from behind

Front 15

guidance at the midline step 2: switching on repulsion

Back 15

initially axons are attracted by Netrin1 and insensitive to the repulsive action of Slit proteins because they express Robo3 which suppresses the activity of Robo1 and 2.

Hint 15

when they cross the midline axons downregulate expression of Robo3 and increase expr of Robo1 and 2 which allows them to sense the repulsive action of slits

Front 16

commissural axon trajectories: after midline crossing

Back 16

commissural axons turn in an anterior direction in response to an an attractive rostral to caudal decreasing gradient of Wnt however corticospinal tract axons response to Wnt as a repllent and so navigate in an opposite direction

Front 17

growth cone structure:

Back 17

filopodia lamellipodia peripheral and central domains

Front 18

growth cone dynamics:

Back 18

in a constant state of flux- extending and retracting processes, sampling environment cues, and steering in new directions

Front 19

how can guidance cues affect the direction of growth cone advance?

Back 19

by controlling the polymerization that helps drive protrusion of the leading edge of the growth cone

Front 20

what is concentrated at the leading edge of growth cones?

Back 20

a dense meshwork of fibrillar actin (F-actin) 7 nm in diameter; composed of polarized polymers of 42 kD actin monomers

Hint 20

filopodial protrusions contain F-actin

Front 21

mechanisms of growth cone advance and steering

Back 21

filopodial protrusion depends upon actin assembly/disassembly cycle

Hint 21

new actin polymerization helps push it forward while it is simultaneously depolymerized at an equal rate more centrally

Front 22

elongation of existing actin filaments is done how

Back 22

this process is coupled to actinmonomer binding of ATP and delayed ATP hydrolysis

Front 23

retrograde flow AKA treadmilling of actin polymers occurs how

Back 23

through the action of non-muscle myosin including myosin II

Hint 23

myosin is an actin binding protein

Front 24

in the absence of adhesive contacts with the substratum what happens to the growth conee

Back 24

a steady state arises whereby the actin polmerization-depolymerization cycle and treadmilling do lead to advance

Front 25

what heppens if polymerized F actin is linked to a permissive substratum?

Back 25

retrograde F-actin flow rate is less than the rate of growth cone advance

Front 26

Rho family GTPases

Back 26

Rach and Rho are key regulators of actin dynamics

Front 27

extracellular cues that regulate microtubule dynamics

Back 27

microtubule binding proteins CLASP and APC bind to the distal plus end of microtubules and are intracellular targets for guidance cue signaling

Front 28

CLASP

Back 28

stabilizes microtubules and prevents their extension into the growth cone periphery