Identification of a key molecular pathway required for brain neural circuit...( Montral May 15 2009 The research gr...)

Montral, May 15, 2009 The research group of Dr. Frdric Charron, a researcher at the Institut de recherches cliniques de Montral (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, Sbastien 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, Frdric 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 ob
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