[ Back to EurekAlert! ] Public release date: 15-May-2009
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Contact: Olivier Lagueux
olivier.lagueux@ircm.qc.ca
514-987-5555
Institut de recherches cliniques de Montreal

Identification of a key molecular pathway required for brain neural circuit formation

Montréal, May 15, 2009 – The research group of Dr. Frédéric Charron, a researcher at the Institut de recherches cliniques de Montréal (IRCM), has made a discovery which could help treat spinal cord injuries and neurodegenerative diseases. This new finding has been published in the current issue of the prestigious scientific journal Neuron. Patricia T. Yam, Sébastien D. Langlois and Steves Morin, all at the IRCM, are listed as co-authors.

The brain is composed of billions of interconnected neurons. To correctly form neuronal circuits, the developing axons (a long extension of a neuron) require attractive and repulsive molecules to lead them to their appropriate targets. One such molecule is Sonic Hedgehog (Shh). Five years ago, as a postdoctoral fellow in the laboratory of Dr. Marc Tessier-Lavigne at Stanford University, Frédéric Charron discovered that Shh acted as an axonal attractant for brain and spinal cord neurons. "How exactly Shh elicited this effect has remained unknown so far," pointed out Dr. Charron. "The molecular pathway my team discovered provides part of an answer."

Their recent work showed that Shh exerts its attractive effect through a group of molecules called Src family kinases (SFKs) that, until now, were not known to be linked to Shh function. Remarkably, these novel Shh effector molecules are absolutely required for the ability of Shh to guide axons. Connecting axons with an appropriate set of targets is very complex. Inappropriate wiring or damage to these neuronal connections leads to severe abnormalities of the nervous system. "Knowing the effectors of axon guidance molecules such as Shh", adds Dr. Charron, "helps us to understand the molecular mechanisms by which axons reach their target. It paves the way to new therapies to treat spinal cord injuries, neurodevelopmental disorders, and neurodegenerative diseases."

This new discovery was made possible through the invention of a novel technique to control and observe the behavior of axons in response to guidance molecules. A patent application for this technique has been filed recently. This invention is expected to speed up the discovery of drugs that control axon pathfinding.

"Dr. Charron is one of the country's leading newly arrived neuroscientists. This research has important long-term implications for the repair of spinal cord injury: if we knew all of the molecules required to guide axons correctly during spinal cord healing, we would probably know how to heal spinal cord injuries," says Dr. Rod McInnes, Scientific Director of the Canadian Institutes of Health Research Institute of Genetics. "This is beautiful research that adds another major brick to our building a complete understanding of how the spinal cord is made, and how injury of it can be treated."

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This work was supported by grants from the Canadian Institutes of Health Research (CIHR), the Canadian Foundation for Innovation (CFI), the McGill Program in Neuroengineering, the Fonds de recherche en santé du Québec (FRSQ) and the Peter Lougheed Medical Research Foundation.

References for this article are available at: http://www.cell.com/neuron/abstract/S0896-6273(09)00247-5

Dr. Frédéric Charron is Assistant Research Professor IRCM and Director of the Molecular Biology of Neural Development Research Unit at the IRCM. Dr. Charron is also Assistant Professor in the Department of Medicine at Université de Montréal, member of the Centre of Excellence in Neuromics of Université de Montréal (CENUM), member of the McGill Program in Neuroengineering, and Adjunct Professor in the Faculty of Medicine at McGill University. He is a recipient of the Peter Lougheed Medical Research Foundation Award and a New Investigator of the Canadian Institutes of Health Research (CIHR).

Established in 1967, the IRCM (www.ircm.qc.ca) now has 35 research units specialized in areas as diverse as immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry, clinical research and bioethics. It has a staff of more than 450 people. The IRCM is an independent institution, affiliated with the Université de Montréal and has built, over the years, a close collaboration with McGill University.

Information:
Frédéric Charron, Ph. D.
Director of the Molecular Biology of
Neural Development Research Unit, IRCM

Olivier Lagueux
Communications Officer
olivier.lagueux@ircm.qc.ca
514-987-5555
www.ircm.qc.ca



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