Cours: Axon Guidance

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Questions and Answers

Which of the following is NOT a guidance cue for commissural axons?

Semaphorin3A (correct)

Shh

Netrin

BMP7

What is the effect of the roof plate on commissural axons?

Induction

Repulsion (correct)

No effect

Attraction

Which guidance cue is expressed by the floor plate?

Draxin

BMP7

Semaphorin3A

Shh (correct)

What is the effect of Semaphorin3A on DRG axons?

Repulsion (D) Signup and view all the answers

What is the connection between the chemoaffinity hypothesis and the labeled-pathway hypothesis?

The labeled-pathway hypothesis is a more recent development that refines the chemoaffinity hypothesis by specifying the molecular tags involved. (B) Signup and view all the answers

What does Paul Letourneau's observation about axonal pathway selection suggest about the process of axon guidance?

The process of axon guidance is complex and involves a combination of factors, including adhesive strength and the presence of specific molecular cues. (C) Signup and view all the answers

How do guidepost cells contribute to the navigation of axons?

Guidepost cells act as intermediate targets, providing a stepping stone for axons to reach their final destination, similar to landmarks in navigation. (B) Signup and view all the answers

What does the study by Lemmon et al. (1992) suggest about the relationship between adhesion strength and axonal growth?

The strength of adhesion does not necessarily determine axonal growth rate or preference, indicating that other factors are involved. (A) Signup and view all the answers

How can the expression of a guidance receptor change on a growth cone?

All of the above (D) Signup and view all the answers

What is the fundamental principle highlighted by the phrase 'Solve a big problem by cutting it down to little steps' in the context of axon guidance?

Axons rely on a series of intermediate targets, such as guidepost cells, to navigate complex paths. (B) Signup and view all the answers

Which of the following can alter the stability of a protein, according to the text provided?

NrCAM and Gdnf (A), Calpain (C) Signup and view all the answers

Why do axons only turn after contact with the intermediate target?

Because the growth cone changes guidance receptors upon contact with the intermediate target (A) Signup and view all the answers

What observation by Roger Sperry forms the basis of the chemoaffinity hypothesis?

Axons possess molecular tags that match specific receptors on their target cells, enabling them to establish the correct connections. (C) Signup and view all the answers

Which of these researchers studied the role of adhesion strength in axon guidance?

Paul Letourneau (D) Signup and view all the answers

Which of the following is NOT a mechanism by which a guidance cue can affect the behavior of an axon?

Changes in the shape of the growth cone (C) Signup and view all the answers

What does the statement 'Inputs from the retina form a topographic map in the tectum' imply about the organization of the nervous system?

The nervous system exhibits a high degree of order and precision, with specific connections responsible for specific functions. (D) Signup and view all the answers

What concept is being referred to by the phrase "Cis- versus trans-interactions can change trans-interactions"?

That the binding states of proteins can influence each other, resulting in changes in the interaction between two proteins (D) Signup and view all the answers

How does miR-124 regulate the responsiveness of young retinal ganglion cells (RGCs) to Sema3A?

miR-124 acts as a repressor, inhibiting the expression of CoREST, which in turn represses Nrp1 and prevents the response to Sema3A. (D) Signup and view all the answers

What is the role of RabGDI in commissural axon guidance?

RabGDI facilitates the trafficking of Robo1 to the growth cone surface, increasing its responsiveness to Slit and promoting the exit of axons from the floor plate. (C) Signup and view all the answers

What is the role of Axonin-1/Contactin-2 in commissural axon guidance?

Axonin-1/Contactin-2 binds to NrCAM, detecting the floor plate and guiding commissural axons through it. (B) Signup and view all the answers

How does Cables1 link Slit/Robo signaling to Wnt signaling?

Cables1 acts as a scaffold protein, bringing together Robo1 and β-Catenin, facilitating the transfer of Abl kinase from Robo1 to β-Catenin. (C) Signup and view all the answers

What is the significance of the change in responsiveness to Sema3A in retinal ganglion cells with age?

It ensures axons are more sensitive to repulsive cues during early development, preventing them from growing into inappropriate areas. (C) Signup and view all the answers

What is the role of phosphorylation of (\beta)-Catenin at tyrosine 489 in commissural axon guidance?

It enhances the sensitivity of the axon to the Wnt gradient, allowing it to follow the correct path. (B) Signup and view all the answers

What is the significance of the shift in the balance between positive and negative signals upon floor-plate contact?

It helps axons avoid getting trapped in the floor plate, promoting their exit to reach their target regions. (D) Signup and view all the answers

Which of the following is NOT a mechanism by which guidance receptors on the growth cone can influence axon guidance?

Modifying the interaction between the receptor and its ligand (B) Signup and view all the answers

What does a change in the guidance receptors on the growth cone primarily impact?

The function of the growth cone (B) Signup and view all the answers

What are the two main mechanisms by which commissural axons are guided along the longitudinal axis of the spinal cord?

Wnt4 and Shh (B) Signup and view all the answers

What happens to the Shh receptor on commissural axons as they cross the midline?

The receptor is switched from Boc/Ptc/Smo to Hhip. (B) Signup and view all the answers

Which of the following guidance cues is responsible for attracting commissural axons along the longitudinal axis of the spinal cord?

Wnt4 (B) Signup and view all the answers

How does Shh influence commissural axon behavior before and after crossing the midline?

Attracts before crossing, repels after crossing. (C) Signup and view all the answers

Which of these are examples of guidance cues that function in short-range guidance of commissural axons?

Contactin-2 (Axonin-1) and Nrp2/Sema3 (B) Signup and view all the answers

What statement about the role of Shh as a morphogen is true?

Shh influences the development of the spinal cord by establishing a gradient that determines cell fate. (C) Signup and view all the answers

What kind of guidance cues are classified as long-range?

Cues that act over large distances, influencing axons from afar. (A) Signup and view all the answers

What is the role of GPC1 in the context of commissural axons?

GPC1 acts as a switch for Shh signaling, mediating the switch in response to Shh. (A) Signup and view all the answers

How does Shh guide postcommissural axons both directly and indirectly?

Shh directly guides axons by binding to receptors on the growth cone, and indirectly by stimulating Wnt signaling. (A) Signup and view all the answers

What is the role of Sfrp1 in the context of axon guidance?

Sfrp1 forms a concentration gradient which influences axon growth. (D) Signup and view all the answers

How does the environment of the intermediate target influence the growth cone's response to guidance cues?

The intermediate target provides signals that directly change the expression of guidance receptors on the growth cone. (D) Signup and view all the answers

Which mechanism is NOT likely to be directly involved in changing a growth cone's response to guidance cues upon contact with the intermediate target?

Changes in protein stability. (C) Signup and view all the answers

What is a likely consequence of changing the expression of guidance receptors on the growth cone?

Changes in the axon's sensitivity to specific guidance molecules. (B) Signup and view all the answers

Which of the following mechanisms is NOT likely to be involved in the regulation of guidance receptor expression on a growth cone?

Changes in the synthesis of new ribosomes for protein translation. (C) Signup and view all the answers

Study Notes

Development of the Nervous System: Axon Guidance

Axon tracts rapidly increase in complexity during early development
Shows diagrams demonstrating the growth and complexity of axon tracts over time (16-36 hours)
Santiago Ramón y Cajal, Paul Weiss, and Roger Sperry are key figures in the history of axon guidance research
Contact guidance by mechanical means was an early, disproven hypothesis.
The chemoaffinity hypothesis, proposed by Roger Sperry, is the currently accepted model.
Inputs from the retina form a topographic map in the tectum
- Diagrams show "Normal" and "Rotated" frog eye connections to the tectum
- Visual stimuli (e.g., a fly) elicit a corresponding response in the tectum according to its location.
Sperry's chemoaffinity hypothesis
- Neural connections are determined by molecular tags on axons and target cells.
What are these molecular tags and how do axons find their target? (This is addressed in further materials)
The labeled-pathway hypothesis is discussed (and further addressed).
Axons use guidepost cells as intermediate targets
Growth cones readily grow onto more attractive substrates
Observations by Paul Letourneau suggest axons select pathways based on adhesive strength
Strength of adhesion does not correlate with growth rate preference for more complex substrates
Adhesion does play a role in axon guidance.
- Diagrams show the various types of axon guidance
Growth cones of PNS (peripheral nervous system) axons collapse upon contact with CNS (central nervous system) axons
- Demonstrates collapse of growth cones via images.
Semaphorin3A repels NGF-dependent sensory axons
- Demonstrated via images.
Axon guidance involves cooperation of attractive and repulsive cues
Information from guidance cues is transmitted to the cytoskeleton via surface receptors.
Molecules act as guidance cues or receptors, determining their attraction/repulsion.
- Question: How many are there?
- Question: Do all axons listen to the same cues?
Axons are guided by positive and negative cues
Commissural neurons in the dorsal spinal cord
Netrin is a chemoattractant for commissural axons
- Diagrams show the action of Netrin on commissural axons.
Is netrin-1 sufficient for long-range guidance of commissural axons?
Netrin is sufficient to attract commissural axons
- Demonstrated via images.
Additional cues, like Shh and VEGF, influence the development of the floor plate and axon growth
Commissural axons are repelled by the roof plate
BMP7 mimics the effect of the roof plate
Draxin is expressed by the roof plate and repels commissural axons
Short-range guidance cues
Interaction between growth cone Axonin-1 and floor-plate NrCAM makes axons enter the floor plate
NrCAM is a binding partner for Axonin-1 in commissural axon guidance
Fasciculation is not required for commissural axon pathfinding in higher vertebrates
Why do commissural axons ever leave the floor plate? (Target)
The intermediate target loses its attractiveness
Commissural axons lose responsiveness to Netrin after contact with the floor plate
The midline glia in the ventral nerve cord is the equivalent of the floor plate in vertebrates
Midline-derived guidance cues in the ventral nerve cord (diagrams)
A screen for midline crossing mutants in Drosophila led to the identification of commissureless and roundabout.
The upregulation of Roundabout expels axons from the floor plate.
Balance between positive and negative signals shifts upon floor-plate contact
RabGDI is required for Robo1 insertion into the growth cone membrane.
Trafficking regulates protein expression on the growth cone
How do axons switch their behavior at an intermediate target? (Mechanisms)
Classical guidance cues for commissural axons
Commissural axons turn rostrally upon floor-plate exit
Wnts are expressed in a decreasing rostral to caudal gradient
Wnt4 is an attractant for post-crossing commissural axons
Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord
Wnt4 attracts and Shh repels postcommissural axons.
Shh acts as a morphogen
Shh acts as a chemoattractant for pre-crossing axons.
Shh acts as a repellent cue for post-crossing commissural axons.
Commissural axons change Shh receptors at the midline
Glypican1 mediates the switch in commissural axon responsiveness to Shh at the midline
Sfrp1 forms a Wnt activity gradient
Shh guides postcommissural axons
Why do axons only turn after contact with the intermediate target?
PlexinA1 is stabilized.
Cis-versus trans-interactions can change trans-interactions.

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Description

Test your understanding of the mechanisms involved in axon guidance. This quiz covers various guidance cues, the role of different cellular components, and important hypotheses related to axonal growth and navigation. Delve deep into the complexities of how axons find their paths during development.