The Tao of Axon Pruning

To attain knowledge, add things every day. To attain wisdom, remove things every day.

Lao Tsu

Apparently our nervous systems develop according to the Chinese philosopher’s principle of being and not being. As our nerve cells grow, they send out long extensions – axons – throughout the developing tissues. And as they reach out, some are also pruned back. The configuration of nerve endings we finally possess depends on both what was added and what was removed.

Which axons will complete their developmental journeys and which will be pruned back? For some, it is simply a matter of fate.

But in the system studied by biochemist Dr. Avraham Yaron and his team, the sensory nerves in the skin, the decision arises from a limited number of neurotrophins – biological “beacons” in the target tissues that guide the growing nerve endings. Though the axons initially receive guidance to help them grow out in the right direction, at some point, they must compete for the scarce neurotrophin signals. Such a signal from a neurotrophin grants a developing axon the “knowledge” it needs to reach its final destination; lack of a signal initiates the “wise” path of pruning. So, what looks like a completely random process is, in fact, a method of attaining the proper, harmonious balance in our nervous systems.

This is the result when neuron pruning is induced in wild-type mice

And the nerve extensions, it turns out, carry the seeds of their own “enlightenment.” The researchers revealed the precise protein that mediates the pruning process. All the growing axons contain an inactive form of this protein; it is the addition of the neurotrophin signal that keeps it from activating.

Before we get carried too far into the realm of philosophical metaphors, we should point out the practical relevance of this research. Scientists refer to the axon pruning process as “remodeling.” In other words, it is not just the number of axons you end up with, but the shape of the nerve network that determines how efficiently communication takes place across that network. And a small but growing body of recent research suggests that such developmental disorders of the nervous system as autism may be tied to problems with the remodeling process. So understanding the exact mechanics of axon pruning could lead to better models of the disorder, better diagnostic tests and, eventually, possibly even treatments.

When the gene for one step in the pruning process is knocked out, this is what you get