Understanding how the nervous system is wired during embryo formation could help promote the reconnection of injured nerves to their target in neurodegenerative diseases, such as Parkinson’s disease, or after an injury, such as a spinal cord lesion. It is with this in mind that a team of researchers from the Institut de recherches cliniques de Montréal (IRCM) / Montreal Clinical Research Institute, led by Frédéric Charron, highlighted a mechanism involved in the formation of brain circuits.
Similarly to electrical cables, nerves are important for connecting together different parts of our body. For example, in order to elicit walking, our brain is connected to our spinal cord, which is connected to our legs. A nerve is composed of many microscopic wires called axons. During embryo formation, axons grow and connect to the appropriate target due to their growth cone, which is a motile structure at the tip of an axon responsible for detecting guidance cues.
One of these guidance cues is Sonic hedgehog (Shh). However, until recently, how Shh works to guide axons remained mostly unknown. Dr. Charron, Full IRCM Research Professor and Associate Research Professor in the Department of Medicine at Université de Montréal, and his team showed that Shh functions by activating a specialized machinery that produces a protein locally in the growth cone, which then makes that growth cone turn. “These results show that growth cones are autonomous and do not need the cell body to be guided. As some of our axons can be longer than one metre, it is speculated that this local machinery makes it easier for a growth cone to respond autonomously and quickly to a guidance cue,” says Dr. Patricia Yam, IRCM Research Associate and co-senior author on the study.
“To use an analogy, let’s say someone wants to build a log cabin deep in the forest. One option is to carry all the logs to the remote location to build the cabin; this requires a lot of work. Another option is to only carry a saw and generate the logs locally, as they are needed to build the cabin. The latter option is obviously easier and more flexible, similarly to what the guidance cue Shh can do in the growth cone, as shown in our study,” concludes Dr. Charron.
About the study
The research project was carried out at the IRCM Molecular Biology of Neural Development research unit by Léa Lepelletier, Sébastien D. Langlois, Christopher B. Kent, Steves Morin, Patricia T. Yam and Frédéric Charron. Kristy Welshhans from Kent State University and
Gary J. Bassel from Emory University School of Medicine were also involved in the study. The research received financial support from the Canadian Institutes of Health Research, the Fonds de recherche Québec – Santé, the Canada Foundation for Innovation and the Canada Research Chairs Program.
About the IRCM
Founded in 1967, the Institut de recherches cliniques de Montréal (IRCM) / Montreal Clinical Research Institute is a non-profit organization that conducts fundamental and clinical biomedical research in addition to training high-level young scientists. With its cutting-edge technology facilities, the institute brings together 33 research teams, which work in cancer, immunology, neuroscience, cardiovascular and metabolic diseases, systems biology and medicinal chemistry. The IRCM also operates a research clinic specialized in hypertension, cholesterol, diabetes and cystic fibrosis, as well as a research centre on rare and genetic diseases in adults. The IRCM is affiliated with the Université de Montréal and associated with McGill University. Its clinic is affiliated with the Centre hospitalier de l’Université de Montréal (CHUM). The IRCM is supported by the Ministère de l’Économie, de la Science et de l’Innovation (Quebec ministry of Economy, Science and Innovation).
Source:
Anne-Marie Beauregard, Communication Advisor
Institut de recherches cliniques de Montréal (IRCM) / Montreal Clinical Research Institute
514-987-5555 | anne-marie.beauregard@ircm.qc.ca
