Identification of a key gene required for brain neural circuit formation

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.”