Researchers reveal signaling mechanism for proper guidance of developing axons

An international team of scientists led by Université de Montréal medical professor Frédéric Charron, director of the molecular biology of neuronal development research unit of the UdeM-affiliated Montreal Clinical Research Institute (IRCM), has discovered an important interaction between the WAVE complex and the Boc receptor, essential for axon guidance.

Axon guidance is the pathfinding step that enables axons—the longest part of a neuron, through which the nerve impulse is propagated outside the cell—to be correctly directed to their target. Their movement is enabled by the actin cytoskeleton, a network of proteins in cells which, similar to the human skeleton, provides structure and support.

Published in November in iScience, Charron’s extensive work shows that the WAVE complex, already known for its role in actin cytoskeleton assembly, interacts directly with Boc, a receptor crucial for signaling induced by the guidance molecule Sonic hedgehog (Shh). This interaction is vital for proper guidance of developing axons.

A guidance signal that attracts

During embryonic development, Shh acts as a guidance signal, attracting axons. The team led by Charron, who also holds the Canada Research Chair in Developmental Neurobiology, had previously demonstrated that the Boc receptor mediates this attraction.

However, the underlying mechanisms were not yet fully understood. This research identifies the WAVE complex as a key player in this process. The WAVE complex, through its interaction with Boc, facilitates the cytoskeletal changes required for axon guidance.

Understanding the molecular mechanisms of axon guidance is crucial to developing therapeutic strategies for neurological disorders. Axon guidance defects can lead to severe problems in the development of the nervous system and contribute to various neurological diseases.

Charron and his study’s collaborators in the U.S. and Germany believe that the identification of the WAVE complex as a critical component in Shh-mediated axon guidance opens up new avenues of research and potential treatments.