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What Is Axon Guidance?

A diagram of different types of neurons, including the axons.
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  • Written By: Meg Higa
  • Edited By: Shereen Skola
  • Last Modified Date: 28 June 2014
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Researchers of human physiology have long known that individual nerve cells, also called neurons, are one of the few cells with the ability to regenerate and self-repair. A nerve cell transmits electrical signals via a long, structural protrusion called its axon. When the axon is injured and completely severs, it begins regenerating and growing toward its previously severed other end. By the turn of the 21st Century, much had been learned about the process, but with limited scientific certainty about the exact mechanism, researchers have dubbed this narrowly targeted field of study, axon guidance.

A nerve cell can be described as having three parts. The main body of the cell, called its soma, has many small, branching protrusions called dendrites which pick up the chemical signatures of an electrical signal. To relay the signal, the soma generates an electrical charge that pulses along another singular protrusion, its axon. Whether it's a motor neuron to control muscle movement, or a sensory neuron to detect a skin tickle, a single microscopically thin axon can reach from a toe to the base of the spine. The fundamental question of axon guidance is how a nerve’s growing, actively elongating axon finds its way to the correct, extremely precise, terminal place.

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The mistaken guess that a cell is internally pre-programmed is dismissed, as every cell contains the same set of genetic instructions. The conclusion is that it must be an external signal, mostly likely chemical, that an axon is homing into. Consequently, the tip of a growing axon must contain a receptor to recognize the signal. Researchers believe that this is one of the main drivers of axon guidance.

A growing or regenerating axon’s tip is called its growth cone. This has been found to develop unusual, very small protrusions called filopodia which make contact with surrounding tissue. They are searching for chemicals called cell adhesion molecules, mostly found on the cell walls of certain types of tissue, which signal the axon to adhere itself in this spot and continue searching. Guided thus, a regenerating axon can grow as much as 0.08 – 0.2 inches (2-5mm) per day.

Researchers have discovered that each filopodia is, not only attracted to certain chemicals, but also repelled by others. Detection of these chemicals either speeds up or slows down the rate of axon growth, and relative detection from each filopodia therefore results in asymmetric growth. The axon is chemically guided to grow in incrementally corrected directions. One difficulty with this model of axon guidance, however, is that researchers are cataloging numerous biological chemicals to which the growth cone reacts.

Quite naturally, embryology or the study of an organism’s early development, intersects research in axon guidance. One theory derived from observing the eggs of chickens and frogs suggests that axons grow according to a spatial topography. The relative dispersal of chemical cues from the multitude of nearby nerve cells acts as a kind of magnetic alignment to organize the axon’s growth direction. Another theory notes that the bilateral symmetry of most complex animals necessitates that axons encounter decision points, called commisures, to direct them in radically specific directions like right or left. There is evidence of certain types of cells termed guidepost cells that include other growing nerve cells, which have this effect.

The human nervous system can be subdivided into the central nervous system, consisting of the brain and spinal cord, and the peripheral nervous system that branches throughout the body. There is much to learn about how the nerve cells of the brain and spinal cord regenerates and repairs. It’s assumed that better understanding of the more readily observable process of regenerating peripheral nerves will lead to potential therapies for brain and spinal injuries.

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