Unit 1 - Axonal Growth, Synaptogenesis, and Tropism Flashcards
neuronal polarization
first step in neuronal identity and the formation of connections (primary property of all cells)
- neuron starts round with no obvious processes (neurites)
- over time it begins to extend multiple processes and becomes multipolar
- one of these processes become the axon, which then defines the polarity of the neuron
- at the tip of the axon is/are specialized structure(s) called growth cones
axonal growth cone structure, function, and morphological characteristics
specialized motile structure at tip of extending axon
- explores extracellular environment, determines direction of growth, and guides extension of axon
- key decision-making structure in axon pathfinding
- lamellapodium - fan-shaped sheet at tip of axon; contains actin filaments and microtubules
- filopodia - fine processes extending out from lamellapodium; contain actin filaments; form and disappear rapidly
cytoskeletal elements in growth cones
globular actin can be incorporated into filamentous actin at leading edge of filopodium in response to environmental cues
- key to growth cone turning is binding of F-actin binding PRO to F-actin to regulate retrograde flow
- when encountering attractive cue, assembly is increased and retrograde flow slowed, causing turning towards attractive cue (opposite if repulsion)
- microtubules make core of cytoskeleton in axon, and are stable and strong
- modulation of interactions with microtubules modulate stability and turning of axons
what are microtubules and F-actin primarily responsible for?
microtubules: axon elongation
F-actin: direction
cytoskeleton components in growth cones
- F-actin
- tyrosinated microtubles
- acetylated microtubules
discrete regions of growth cones can be detected by different types of actin and tubulin
- F-actin is in lamellipodium and filopodia
- tyrosinated microtubules are in lamellipodia, and around for a shorter amount of time than acetylated
- acetylated microtubules are only in axons
growth cones and “decision points”
growth cone changes shape when they encounter specific environmental cues
4 types of axon guidance molecules
non-diffusible (short-range) 1. contact attraction 2. contract repulsion diffusible (long-range) 3. chemoattraction 4. chemorepulsion
all act in concert to guide axon to appropriate target to ensure accurate guidance
what do attractive and repellent interactions promote in terms of growth cone movement?
attractive: promote actin polymerization in direction of attractive molecules
repellent: promote actin depolymerization and growth cone collapse
are ECM molecules attractive or repellent? what kinds are there?
both PNS (attractive) and CNS (repellent) non-diffusible molecules
- PNS: laminins, collagens, and fibronectin; bind to integrin growth cone receptors to trigger signaling cascades for axon growth and elongation
- CNS: hyaluronan, proteoglycans, and glycoproteins; lacks “typical” matrix molecules of PNS
are cell adhesion molecules attractive or repellent? where are they? how do they work? are they Ca++ independent or dependent? what is the L1 CAM associated with?
attractive non-diffusible molecule; located on surface of growing axons, growth cones, and surrounding cells or targets
- act as ligands and receptors via homophilic binding
- Ca++ independent
- ligand/receptor interaction induces interaction with cytoplasmic kinases in growth cone
- L1 CAM has been associated with fasciculation (bundling) of groups of axons as they grow
are cadherins attractive or repellent? where are they? what do they do? are they Ca++ independent or dependent?
attractive non-diffusible molecule; located on surface of growing axons, growth cones, and surrounding cells or targets
- act as ligands and receptors via homophilic binding
- Ca++ dependent
- ligand/receptor interaction triggers intracellular signaling pathways that lead to actin binding and organization
are semaphorins attractive or repellent? where are they? what do they do? what family are the growth cone receptors?
mostly repellent non-diffusible molecules; can be attractive in some situations
- can be secreted or anchored to the cell surface; secreted forms are attached to cell surface or ECM, so not really diffusible
- receptors on growth cones are plexins; cell surface forms bind directly to plexins, while secreted forms bind neuropilins then complex with plexins
- ligand/receptor interaction results in growth cone collapse and inhibition of axon extension via receptor interaction with intracellular signaling molecules
are ephrins attractive or repellent? what are the classes? what do they do?
repellent non-diffusible molecules, similar to CAMs
- ephrin-A: GPI_linked to cell surface
- ephrin-B: single pass transmembrane PRO
- each class has its own set of receptors on growth cones that are tyrosine kinases
- ephrin interaction with its receptor on the growth cone results in a repellent interaction that collapses the growth cone
ephrins in the optic tectum (superior colliculus)
-differences in anterior and posterior tectum
- in developing brain, axons from the retina make precise connections with optic tectum
- -temporal/lateral retina to anterior tectum
- -nasal/medial retina to posterior tectum
- ephrins A2 and A5 are expressed in anterior-to-posterior gradient with highest concentration at posterior side
- axons from temporal retina are repulsed by ephrin in posterior tectum b/c they express high levels of EphA3 receptor
- axons from nasal retina are blind to ephrin b/c they lack the eph receptor
are netrins attractive or repellent? what secretes them? what happens if it’s knocked out?
attractive or repellent diffusible molecules, depending on receptors expressed on growth cone
- secreted by target cells in midline of embryo
- attractive receptors are members of DCC family
- repellent receptors are members of UNC5 family
- KO eliminates crossing of commisural axons
