Identification of a key gene required for brain neural circuit formation



Director of the Molecular Biology of Neural Development Research Unit at IRCM
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Montréal, October 31, 2006 -- An international team of scientists, lead by Dr. Frederic Charron at the IRCM, and Drs Ami Okada, Sue McConnell, and Marc Tessier-Lavigne in the USA, have made a discovery which could help treat spinal cord injuries and neurodegenerative diseases. This new finding will be published in the next issue of the prestigious scientific journal Nature.

The brain is composed of billions of neurons that must connect their axons with an appropriate set of targets to form the neuronal circuits that underlie its function. Developing axons are guided to their targets by attractive and repulsive guidance molecules. Inappropriate wiring or damage of these neuronal connections leads to severe abnormalities of the nervous system.

Three years ago, while he was a postdoctoral fellow in the laboratory of Dr. Marc Tessier-Lavigne, Dr. Charron discovered that Sonic Hedgehog (Shh) is an axonal attractant for brain and spinal cord neurons. However, the mechanism by which Shh elicited this effect remained unknown. The recent work of Dr. Charron, performed in close collaboration with Dr. Ami Okada and the teams of Drs. Sue McConnell and Marc Tessier-Lavigne, at Stanford University and Genentech, respectively, showed that Shh exerts its attractive effect through a novel receptor named Boc. Remarkably, this novel Shh receptor is absolutely required for the axon guidance role of Shh and the role of Shh in brain neural circuit formation.

"The findings of Dr. Charron and his team are of great relevance in developmental neurobiology and our understanding of normal brain development. This research could eventually have an impact on our understanding of neurodevelopmental disorders," says Dr. Rémi Quirion based in Montréal and Scientific Director of the Canadian Institutes of Health Research Institute of Neurosciences, Mental Health and Addiction. "No matter how specialized research findings may be, the knowledge we gain from them, holds the key to improved health and quality of life for Canadians and people throughout the world afflicted by neurodevelopmental disorders," adds Dr. Quirion.

In addition to helping us understand the immense complexity underlying the wiring of the nervous system, the Dr. Charron's research will also help to identify novel strategies to promote the proper guidance and wiring into neural circuits of axons damaged by neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, or by brain and spinal cord injuries.

This work will be published only a year after Dr. Charron established his laboratory at the Institut de recherches cliniques de Montréal (IRCM).

"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'd 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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The paper will appear online November 1st, 2006 and is available at http://dx.doi.org/10.1038/nature05246 .

Dr. Charron is a recipient of the Peter Lougheed Medical Research Foundation Award and is a New Investigator of the Canadian Institutes of Health Research (CIHR). He his also Director of the Molecular Biology of Neural Development Research Unit at IRCM and Assistant Professor at the Université de Montréal. The work performed by Dr. Charron and his team was funded by the Canadian Institutes of Health Research (CIHR), the Mabel and Arnold Beckman Foundation, the Fonds de recherche en santé du Québec (FRSQ) and the Peter Lougheed Medical Research Foundation.

The IRCM (www.ircm.qc.ca) is recognized as one of Canada's top-performing research centre. Its mission is to bring the benefits of research to the patient, promote disease prevention, and train the next generation of front-rank scientists. The IRCM, which is affiliated with the Université de Montréal, currently houses 37 research units and employs nearly 450 people.


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