An IRCM Breakthrough Reveals Crucial Interactions for Neuronal Development
Photo: Dr. Frédéric Charron and Dr. Nursen Balekoglu
A team led by Dr. Frédéric Charron, Director of the Molecular Biology of Neuronal Development Research Unit at the Montreal Clinical Research Institute (IRCM), in collaboration with researchers from Toronto, the U.S. and Germany, discovered an important interaction between the WAVE complex and the Boc receptor, which is essential for axon guidance. Axon guidance is the pathfinding step that enables axons to be correctly directed to their target.
The actin cytoskeleton is a network of proteins in cells which, like the human skeleton, provides a support structure and enables axons’ movement. Dr. Charron's extensive work shows that the WAVE complex, already known for its role in actin cytoskeleton assembly, interacts directly with Boc, a receptor that is crucial for signalling induced by the guidance molecule Sonic hedgehog (Shh). This interaction is vital for proper guidance of developing axons.
In Depth
During embryonic development, Shh acts as a guidance signal, attracting axons. Charron's team (also a Research Professor in the Department of Medicine at the Université de Montréal) 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.
Why It's Important
Understanding the molecular mechanisms of axon guidance is crucial to developing therapeutic strategies for neurological disorders. Defects in axon guidance can lead to severe problems in the nervous system’s development and contribute to various neurological diseases. The identification of the WAVE complex as a critical component in Shh-mediated axon guidance opens up new research avenues and potential treatments.
“The challenge of understanding neurological diseases requires continued fundamental research such as that of Dr. Charron and his collaborators. By innovating once again, this laboratory is bringing us closer to new therapeutic options for extremely debilitating diseases,” said Dr. Jean-François Côté, President and Scientific Director of the IRCM.
Collaborators and Acknowledgements
This research was carried out by Nursen Balekoglu, Jean-François Michaud, Rachelle Sauvé, Kaiyue Zhang, Patricia Yam and Frédéric Charron of the IRCM, with significant contributions from Kehinde Ayinde, Yijun Liu, Daniel Kramer, and Baoyu Chen of Iowa State University, Sichun Lin and Stéphane Angers of the University of Toronto, and Anika Steffen and Theresia Stradal of the Helmholtz Centre for Infection Research. The study was funded by the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI) and the National Institutes of Health (NIH).
Dr. Frédéric Charron holds the Canada Research Chair in Developmental Neurobiology.
Full article: https://www.cell.com/iscience/fulltext/S2589-0042(24)02558-6
