Scientists discover key step in the development of nerve cells controlling autonomic functions

07/13/04

McGill Scientists identify gene important for nerve cells controlling heart, respiratory and digestive functions

Montreal, July 13, 2004. Scientists at the Montreal Neurological Institute at McGill University have discovered a gene that is necessary for the correct development of the part of the brain that controls autonomic functions such as heart rate, bronchial dilation and gut peristalsis. In a study published in the Proceedings of the National Academy of Sciences of the USA, Dr. Stefano Stifani and colleagues have demonstrated for the first time that disruption of this gene causes a dramatic loss of these particular nerve cells.

During the development of the nervous system, there are a number of critical events that generate different types of nerve cells in particular locations of the brain and at particular times. "We found that specific types of hindbrain visceral motor nerve cells do not develop when the function of a gene called Runx1 is disrupted in mice, while other types of nerve cells develop normally", explained Dr. Stefano Stifani, Associate Professor of Neurology and Neurosurgery and Anatomy and Cell Biology. "This has never been shown before and it is an important step in understanding how these nerve cells form during normal development."

The hindbrain visceral motor nerve cells normally control the ability to maintain a stable internal environment in response to internal or external influences. Problems associated with their development or function could have important implications for the control of vital body functions such as blood pressure, heart rate, and electrolyte balance.

These results describe a new function for Runx1, which has a well documented role in the development of blood cells. In humans, Runx1 is called AML1. AML1 is the most frequent target of chromosomal translocations that cause acute myeloid leukemia. "This is a significant finding as it suggests for the first time that similar mechanisms involving Runx1 play roles in motor nerve cell and blood cell development and importantly it provides a new avenue of research into the mechanisms that control brain development", said Dr. Freda Miller, Senior Scientist, Hospital for Sick Children in Toronto.

"We believe that Runx1 plays very important roles in promoting the development and survival of those specific hindbrain motor nerve cells", said Dr. Stifani. "Further research will clarify the mechanisms that control the formation and functions of those cells and will help us to understand how other types of nerve cells of the brain and spinal cord are generated during development."

The paper can be viewed online at http://www.pnas.org/cgi/content/abstract/0400768101v1. PNAS is one of the world's most-cited multidisciplinary scientific serials. PNAS Online receives nearly 4 million hits per month.

This research was supported by the Neuromuscular Research Partnership, an initiative of ALS Canada, Muscular Dystrophy Canada, and the Canadian Institutes of Health Research (CIHR).

Dr. Stefano Stifani is an Associate Professor in the Departments of Neurology and Neurosurgery and Anatomy and Cell Biology at McGill University. He is a researcher in the Centre for Neuronal Survival at the Montreal Neurological Institute (MNI), a William Dawson Scholar (McGill University) and Chercheur Boursier Senior of the Fonds de la Recherche en Santé du Québec. Prior to coming to the MNI in 1994, he conducted his postdoctoral training at the Yale University School of Medicine for three years where he discovered novel proteins involved in the regulation of mammalian neural development. Dr. Stifani's research aims to clarify the events that underlie neuronal birth and survival in both the developing and adult nervous system. His studies have led to the characterization of crucial mechanisms controlling nerve cell differentiation and uncovered new protein functions during neurogenesis. The ultimate goal of his research program is to provide strategies to manipulate multipotent neural progenitor/stem cells and facilitate the design of approaches that may promote the repair of the adult nervous system in response to trauma or disease.

The CIHR (http://www.cihr-irsc.gc.ca/) is Canada's premier agency for health research. Its objective is to excel, according to internationally accepted standards of scientific excellence, in the creation of new knowledge and its translation into improved health for Canadians, more effective health services and products and a strengthened health care system. CIHR's Institute of Neurosciences, Mental Health and Addiction supports research to enhance mental health, neurological health, vision, hearing, and cognitive functioning and to reduce the burden of related disorders through prevention strategies, screening, diagnosis, treatment, support systems, and palliation.

The Montreal Neurological Institute (www.mni.mcgill.ca) is a McGill University (www.mcgill.ca) research and teaching institute, dedicated to the study of the nervous system and neurological diseases. Founded in 1934 by the renowned Dr. Wilder Penfield, the MNI is one of the world's largest institutes of its kind. MNI researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders.

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