Annexe: Axonal Guidance Mechanisms

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Questions and Answers

Which of the following molecules are not a part of the dorsal guidance system?

Draxin

VEGF (correct)

netrin (correct)

BMP7

What type of signal is Shh during the axonal guidance process?

Neither attractive nor repulsive

Both attractive and repulsive (correct)

Attractive

Repulsive

What is the role of the floor plate in axonal guidance?

To act as a source of only repulsive signals

To act as a barrier to axonal crossing

To act as a source of only attractive signals

To act as a source of both attractive and repulsive signals (correct)

What is the purpose of axonal crossing?

To allow for communication between the two sides of the spinal cord (C) Signup and view all the answers

What does Sfrp do in the context of axonal guidance?

It inhibits the activity of Wnt (A) Signup and view all the answers

How does Shh modulate Wnt activity?

By shaping the Wnt gradient in an Sfrp-dependent manner (A), By regulating Fzd3 surface expression in a Shisa2-dependent manner (C) Signup and view all the answers

Which of the following molecules are involved in the guidance of commissural axons towards the floor plate?

Netrin, Shh, VEGF (D) Signup and view all the answers

Which molecule binds to Robo1 in preference to N-Slit in the absence of Dscam?

Dscam1 (A) Signup and view all the answers

What role does FLRT3 play in thalamocortical axon guidance?

FLRT3 increases the expression of Dcc, a netrin receptor, in rostral thalamocortical axons. (A) Signup and view all the answers

How does the expression of FLRT3 and Robo1 influence the response of thalamocortical axons to netrin?

FLRT3 and Robo1 enhance the attraction of axons to netrin, promoting rostral movement. (C) Signup and view all the answers

Which of the following molecules is NOT involved in the guidance of thalamocortical axons?

FGF (A) Signup and view all the answers

What is the role of Sema3B and Npn-2 in axon guidance?

They are involved in midline crossing by commissural axons in the spinal cord and brain. (B) Signup and view all the answers

What is the significance of the observed difference in axonal behaviour in the presence of netrin versus the combination of netrin and Slit?

This highlights the importance of the spatial and temporal coordination of different guidance cues in axonal navigation. (D) Signup and view all the answers

Which of the following statements about Robo1 is TRUE?

Robo1 is a receptor for Slit, repelling axons from Slit gradients. (D) Signup and view all the answers

Which of the following is a key reason for the complexity of neural circuits?

The regulation of signaling pathways and the coordination of various guidance cues and receptors. (B) Signup and view all the answers

Which of the following molecules has been identified as an alternative receptor for Slit?

Plexin A1 (C) Signup and view all the answers

How does Shh influence Wnt signaling?

Shh inhibits Wnt signaling through Sfrp and Shisa2. (D) Signup and view all the answers

Which of the following molecules is NOT directly involved in the guidance of commissural axons towards the floor plate?

TAG-1 (B) Signup and view all the answers

How does Robo3 modulate the attraction of axons by netrin?

Robo3 interacts with Dcc and reduces its affinity for netrin. (C) Signup and view all the answers

Which protein directly interacts with Sema6A to modulate its repulsive response?

Plexin-A4 (A) Signup and view all the answers

In which of the following scenarios does Sfrp play a role?

Sfrp regulates the activity of ADAM proteins and influences the interaction between cell adhesion molecules. (C) Signup and view all the answers

What is the primary function of the molecule FLRT3 during axonal guidance?

Determining Netrin-1 attraction in developing axons (C) Signup and view all the answers

What is the role of the molecule Sonic Hedgehog (Shh) in axonal guidance?

Guiding axons via zipcode binding protein 1-mediated local translation (B) Signup and view all the answers

Which of the following is NOT a known mechanism of crosstalk between different axon guidance receptors?

Plexin A1 interacts with Slit and promotes the repulsion of axons. (D) Signup and view all the answers

Which of the following pathways involves a synergistic interaction between netrin and Shh?

The attraction of axons to the midline in flies. (A) Signup and view all the answers

Which of the following molecules functions as a receptor for Netrin-1 in commissural axon pathfinding?

DSCAM (D) Signup and view all the answers

Which mechanism is responsible for the sorting of axons in the optic tract by the molecule Hermes?

Post-transcriptional regulation of Neuropilin 1 (C) Signup and view all the answers

What is the role of RNA-binding proteins in axonal guidance?

Regulating the translation of guidance molecules (A) Signup and view all the answers

Which of the following molecules is directly involved in commissure formation in the mammalian forebrain?

TAG-1 (A) Signup and view all the answers

Which molecule acts as a gatekeeper between the central and peripheral nervous systems?

Semaphorin6A (A) Signup and view all the answers

What is the role of Ryk in axonal guidance?

It acts as a receptor for the Wnt5a protein and is involved in guiding axons to the contralateral side of the corpus callosum. (B) Signup and view all the answers

Which of the following molecules is involved in the regulation of Drosophila brain wiring?

Slit (A) Signup and view all the answers

What is the main function of the Frazzled/DCC receptor in axon guidance?

Its intracellular domain functions as a transcription factor necessary for guiding commissural axons. (A) Signup and view all the answers

What is the role of Nectin-like molecules/SynCAMs in axonal guidance?

They are involved in post-crossing commissural axon guidance, ensuring proper navigation of axons after they cross the midline. (A) Signup and view all the answers

Which of the following proteins is a negative regulator of Slit responsiveness?

Robo3 (D) Signup and view all the answers

Which of the following molecules is required for the growth and guidance of mouse retinal ganglion cell axons?

Shh (B) Signup and view all the answers

What is a significant challenge when studying axonal guidance during embryonic development in mammals?

The precise temporal control of experiments during embryonic development. (B) Signup and view all the answers

In what aspect of axonal guidance research does in vitro experimentation fall short?

Inability to mimic the complexity of cell-cell interactions in developing tissue. (C) Signup and view all the answers

Which of the following techniques is becoming increasingly useful for visualizing the relationship between surface receptors and the cytoskeleton?

High-resolution imaging techniques. (C) Signup and view all the answers

What is the primary reason why diverse animal models are important for studying axonal guidance?

To account for the different strengths and weaknesses of each model system. (A) Signup and view all the answers

How does the research by Bourikas et al. (2005) contribute to our understanding of axonal guidance?

It demonstrates the role of Sonic hedgehog in guiding commissural axons in the spinal cord. (A) Signup and view all the answers

Based on the discussions, how does the research by Brignani and Pasterkamp (2017) relate to understanding axonal guidance?

It sheds light on the specific mechanisms of axonal wiring in the developing midbrain dopamine system. (D) Signup and view all the answers

What is a key takeaway from the research by Brittis et al. (2002) regarding axonal guidance?

Axonal protein synthesis plays a role in localized regulation at an intermediate target. (D) Signup and view all the answers

The research by Bron et al. (2007) focuses on which aspect of axonal guidance?

The role of boundary cap cells in constraining spinal motor neuron somal migration. (A) Signup and view all the answers

Study Notes

Understanding Axon Guidance

Axons extend to reach targets during nervous system development, forming functional circuits
Faulty circuit assembly/disintegration causes nervous system disorders
Molecular mechanisms guiding axons and neural circuit formation are of interest to developmental neuroscientists and for understanding neural disorders
Axons express guidance receptors on their growth cones
Axons navigate using attractive and repulsive guidance information in their environment
Axon guidance molecules are attractive or repulsive
Cooperation of long- and short-range guidance cues is needed for axon navigation to target cells
Intermediate targets during axon navigation provide important guidance and prepare axons for the next stage of their journey
Axonal navigation at choice points remains poorly understood
A switch in responsiveness of growth cones from attraction to repulsion is needed to reach final targets
Timing of this switch is critical for successful target contact

Axon Guidance in the Spinal Cord

Commissural neurons, especially dl1 neurons, have been extensively studied
These axons cross the midline and navigate to the contralateral side via the floor plate
Long-range cues and receptors control different stages of navigation
Netrin 1 attracts dI1 axons to the floor plate, via a concentration gradient
Recent studies question the floor plate as the source of netrin in favor of precursor cells in the central canal
Guidance cues like netrin, Shh, and VEGF also attract axons to the floor plate
BMP7 and Draxin are long-range repellents that push axons away from the roof plate.
Short-range guidance cues control navigation at the floor plate
Cntn2 and NrCAM interact to allow axons to enter the floor plate
Slit/Robo1 interactions expel axons from the floor plate
Sema3 is a repellant after crossing
Wnt (attractive) and Shh (repulsive) gradients help axons turn rostrally after crossing
These molecular mechanisms are conserved in the brain

Axon Guidance in the Brain

Molecular mechanisms conserved in the brain
Slit/Robo signaling is involved in the development of the corpus callosum and other commissures, similar to in spinal cord
Class-3 semaphorins and neuropilins regulate midline crossing at the chiasm
Netrin and Slit gradients affect thalamocortical connections
Membrane-bound class-6 semaphorins, plexins and IgSF-CAMs influence visual system axon pathfinding

Regulation of Axon Guidance Receptors

Changes in transcription, translation, and post-translational modifications regulate receptor expression at choice points
Time and internal timers regulate receptor function

Complexity of Axon Guidance

Many molecules and receptors are needed for complex neural circuit formation
Fine-tuning of responsiveness is necessary for proper circuit development
Research is ongoing to fully understand the mechanisms for neural circuit formation

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Description

Test your knowledge on the mechanisms of axonal guidance, including the role of various molecules like Shh, Robo1, and FLRT3. Understand the significance of these components in guiding axons to their targets and the interactions between different signaling pathways. This quiz covers key concepts related to the dorsal guidance system and its components.