Enzymes linked to cell death play key role in structural dynamics of neuronal axons

Feb 07, 2014
Figure 1: Young visual-system axon arbors (top) show localized caspase activation at branch points (green and blue), while older axons do not show caspase activation (bottom). Credit: D. S. Campbell & H. Okamoto

Strict regulation of axon branching and synapse formation is critical for the correct development of the embryonic nervous system, and dysfunction in these processes can lead to neurodevelopmental and neurodegenerative disorders. Douglas Campbell and Hitoshi Okamoto from the RIKEN Brain Science Institute in Wako have now found that the activity of enzymes called caspases in the visual system of zebrafish embryos contributes to the dynamic addition and retraction of new branch tips at the ends of developing axons.

Caspases are involved in a form of known as apoptosis. However, their function in structurally complex cells such as neurons, which have multiple compartments including dendrites, an axon and a cell body, could vary depending on where in the cell they are localized.

Using a fluorescence tracking system that senses activity, and taking advantage of the transparency of the zebrafish embryo for imaging, Campbell and Okamoto observed that high caspase activity occurred in axons at a point in development when visual-system axons are known to be highly dynamic. In embryos at a later developmental window when axons are known to be stable, axons were found to display lower caspase activity (Fig. 1).

By examining branching locations over time, Campbell and Okamoto found that the regions that would soon generate a new branch point exhibited increased caspase activation compared with regions that did not branch. They showed that reducing caspase expression in neurons led to enhanced stability, not only of axons but also of synaptic sites within the axons. These findings suggest that caspase expression allows the to remain morphologically flexible.

Many ligand–receptor systems, such as the ligand Slit, and its corresponding receptor, Robo, play an important role in regulating axon morphology during development. A previous study by Campbell and his colleagues showed that loss of Slit or Robo function could result in a more stable axonal morphology, suggesting that the Slit–Robo ligand–receptor system may modulate caspase signaling in order to affect the dynamics of axon branching and . In zebrafish embryos with reduced Slit or Robo signaling, there was no caspase activation at axon branch points, providing evidence that caspases are activated after the induction of slit–robo signaling.

"Dysregulation of caspase activity could be crucial to the initiation of neurodegeneration. Identification of the mechanisms of caspase activation may therefore be relevant to understanding these disorders," explains Campbell.

Explore further: A triangular protein pump

More information: Campbell, D. S. & Okamoto, H. "Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization." The Journal of Cell Biology 203, 657–672 (2013). dx.doi.org/10.1083/jcb.201303072

Related Stories

How the brain makes myelination activity-dependent

Jan 10, 2014

(Medical Xpress)—A major question regarding how axons acquire a coat of myelin, is the role of spiking activity. It is known that in culture systems oligodendroctyes will at least try to wrap anything ...

Recommended for you

Waiting to harvest after a rain enhances food safety

59 minutes ago

To protect consumers from foodborne illness, produce farmers should wait 24 hours after a rain or irrigating their fields to harvest crops, according to new research published in the journal Applied and Environmental Microbiology.

A triangular protein pump

5 hours ago

Ludwig Maximilian University of Munich researchers have elucidated the structure of a molecular machine with an atypical triangular shape that is involved in peroxisome biogenesis, and characterized its conformation ...

Researchers discover new mechanism of DNA repair

Jul 03, 2015

The DNA molecule is chemically unstable giving rise to DNA lesions of different nature. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed.

Stopping Candida in its tracks

Jul 03, 2015

Scientists are one step closer to understanding how a normally harmless fungus changes to become a deadly infectious agent.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.