XTRPC1-dependent chemotropic guidance of neuronal growth cones

Nat Neurosci, 2005 · DOI: 10.1038/nn1459 · Published: June 1, 2005

Simple Explanation

Axons, the long, slender projections of nerve cells, are guided to their targets in the developing nervous system by chemical cues. These cues can either attract or repel the growing tip of the axon, called the growth cone. Calcium ions play a crucial role in translating these guidance signals into changes in the growth cone's direction. Specifically, increases in calcium levels inside the growth cone, originating from both internal stores and influx from outside the cell, are essential for this process. This study investigates the role of a particular calcium channel, XTRPC1, in the growth cone's response to various guidance cues. The findings show that XTRPC1 is necessary for the growth cone to properly respond to certain attractive and repulsive cues, suggesting it is a key player in axon guidance during development.

Study Duration

Not specified

Participants

Xenopus spinal neurons

Evidence Level

In vitro and in vivo study

Key Findings

1
XTRPC1 is required for the proper growth cone turning responses of Xenopus spinal neurons to microscopic gradients of netrin-1, brain-derived neurotrophic factor (BDNF), and myelin-associated glycoprotein (MAG).
2
Interfering with XTRPC1 function, either by reducing its expression or using dominant-negative mutants, abolishes MAG-induced repulsion.
3
XTRPC1 is essential for the midline axon guidance of commissural interneurons in the developing Xenopus spinal cord.

Research Summary

This study investigates the role of XTRPC1, a calcium channel, in neuronal growth cone guidance in Xenopus spinal neurons. The findings demonstrate that XTRPC1 is required for growth cone turning responses to specific guidance cues like netrin-1, BDNF, and MAG, but not semaphorin 3A. In vivo experiments show that XTRPC1 is also essential for midline axon guidance of commissural interneurons in the developing Xenopus spinal cord.

Practical Implications

Understanding Axon Guidance

Provides insights into the molecular mechanisms that govern axon guidance during neural development.

Potential Therapeutic Target

Suggests that TRPC channels could be potential therapeutic targets for promoting axon regeneration in the injured adult CNS.

Role of Calcium Signaling

Highlights the importance of calcium signaling, specifically through TRPC channels, in mediating neuronal responses to guidance cues.

Study Limitations

1
The study focuses on Xenopus spinal neurons, and the findings may not be directly applicable to other species or neuronal types.
2
The precise mechanisms by which guidance cues activate XTRPC1 remain to be fully elucidated.
3
Future mosaic analysis will be needed to prove that the observed defects are stringently cell-autonomous in vivo.

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