c-Jun N-terminal Kinase 1 (JNK1) Is Required for Coordination of Netrin Signaling in Axon Guidance

Journal of Biological Chemistry, 2013 · DOI: 10.1074/jbc.M112.417881 · Published: January 18, 2013

Regenerative Medicine Neurology Genetics

Simple Explanation

This research investigates the role of JNK1, a type of protein, in axon guidance, which is how nerve cells find their way during development. The study found that JNK1 is essential for Netrin signaling, a process that helps axons grow and navigate. The researchers discovered that Netrin-1, a key molecule in axon guidance, increases JNK1 activity in nerve cells. This activation is enhanced when other molecules, DCC and DSCAM, are also present, suggesting they work together. Furthermore, blocking JNK signaling disrupts Netrin-1's ability to guide axons. This indicates that JNK1 is a crucial component in the signaling pathway that allows axons to respond to Netrin-1 and grow in the right direction.

Study Duration

Not specified

Participants

Primary neurons from E15 cortexes, E11 mouse spinal cords, E13 mouse embryos, chick embryos, HEK293 cells

Evidence Level

Not specified

Key Findings

1
Netrin-1 increases JNK1 activity, but not JNK2 or JNK3, in the presence of DCC or DSCAM, and expression of both further enhances Netrin-1-induced JNK1 activity in vitro.
2
Inhibition of JNK signaling, either chemically or by blocking its upstream activator, blocked Netrin-1-induced JNK1 activation.
3
Knockdown of JNK1 in ovo caused defects in spinal cord commissural axon projection and pathfinding.

Research Summary

This study demonstrates that JNK1 is a key component in Netrin signaling, which is crucial for axon guidance during nervous system development. The researchers found that Netrin-1 activates JNK1 in neurons, and this activation is enhanced by the presence of DCC and DSCAM. Blocking JNK1 activity disrupts Netrin-1-mediated axon guidance. In vivo experiments showed that JNK1 is required for proper commissural axon projection and pathfinding in the developing spinal cord.

Practical Implications

Understanding Neuronal Development

The findings contribute to a better understanding of the molecular mechanisms underlying neuronal circuit formation in the developing nervous system.

Potential Therapeutic Targets

Identifying JNK1 as a key player in Netrin signaling could open new avenues for therapeutic interventions targeting axon guidance-related disorders.

Drug Development

The study suggests that modulating JNK1 activity could be a potential strategy for promoting axon regeneration after injury.

Study Limitations

1
The study primarily focuses on JNK1, while other JNK isoforms may also play a role.
2
The research relies on in vitro and in vivo experiments, and further studies are needed to confirm the findings in more complex models.
3
The precise mechanisms by which JNK1 coordinates DCC and DSCAM signaling require further investigation.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine