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

    MONTREAL, May 15 /CNW Telbec/ - 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
    This work was supported by grants from the Canadian Institutes of Health
Research (CIHR), the Canada 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:
    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 ( 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.

For further information:

For further information: Frédéric Charron, Ph. D., Director of the
Molecular Biology of Neural Development Research Unit; Olivier Lagueux,
Communications Officer,, (514) 987-5555,

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Institut de recherches cliniques de Montréal (IRCM)

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