June 14, 2011 A scientific breakthrough by researchers at the Institut de recherches cliniques de Montréal (IRCM) has been published in Developmental Cell, a scientific journal of the Cell Press group. Led by Dr. Frédéric Charron, the team of scientists discovered a new requirement for the proper functioning of the Sonic Hedgehog protein.
Sonic Hedgehog belongs to a family of proteins that gives cells the information needed for the embryo to develop properly. It plays a critical role in the development of many of the body's organs, such as the central nervous system. Malfunctions of these proteins are associated with many diseases including cancer.
"On one hand, certain molecules travel through our organs (in this case, Sonic Hedgehog) and transmit signals to cells with information on how they should function," explains Luisa Izzi, postdoctoral fellow in Dr. Charron's laboratory and co-first author of the article. "On the other hand, our cells have receptors to receive these signals. The receptors then instruct the cell's DNA as to which genes to turn on or off in order to perform its function."
The team studied the interactions between the Sonic Hedgehog molecule and the recently-identified receptors Boc, Cdon and Gas1, all found on the surface of cells. "Our research showed, unexpectedly, that these receptors are essential for the transmission of the hedgehog molecule's signal," adds Martin Lévesque, an alumnus from Dr. Charron's research unit and co-first author of the article.
"Disrupting the transmission of the Sonic Hedgehog signal can lead to diseases," says Dr. Charron, Director of the IRCM's Molecular Biology of Neural Development research unit. "A better knowledge of the receptors Boc, Cdon and Gas1 might in turn help our understanding of pathologies associated with defective Sonic Hedgehog signalling. Our results could also lead to new avenues for the treatment of certain diseases such as cancer."
According to the Canadian Cancer Society, an estimated 251,900 new cases of cancer and 75,000 deaths caused by the disease will occur in Canada in 2011. In 2007, cancer surpassed cardiovascular disease as the leading cause of death in Canada.
Research carried out in Dr. Charron's laboratory was funded by the Canadian Cancer Society, the Fonds de recherche en santé du Québec (FRSQ), and the Canadian Institutes of Health Research (CIHR).
In addition to directing this research project, Dr. Charron and his team participated in a second study led by Dr. Benjamin L. Allen from the University of Michigan Medical School. This second study, also to be published in the June 14th issue of Developmental Cell, examined the role of the same receptors (Boc, Cdon and Gas1) in a different system and confirmed the results found at the IRCM. Including these two studies, Dr. Charron's team have published three new discoveries in the past two weeks in Developmental Cell and Neuron.
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- Luisa Izzi, Martin Lévesque, Steves Morin, Dominique Laniel, Brian C. Wilkes, Frédéric Mille, Robert S. Krauss, Andrew P. McMahon, Benjamin L. Allen, Frédéric Charron. Boc and Gas1 Each Form Distinct Shh Receptor Complexes with Ptch1 and Are Required for Shh-Mediated Cell Proliferation. Developmental Cell, 2011; 20 (6): 788-801 DOI: 10.1016/j.devcel.2011.04.017
- Benjamin L. Allen, Jane Y. Song, Luisa Izzi, Irene W. Althaus, Jong-Sun Kang, Frédéric Charron, Robert S. Krauss, Andrew P. McMahon. Overlapping Roles and Collective Requirement for the Coreceptors GAS1, CDO, and BOC in SHH Pathway Function. Developmental Cell, 2011; 20 (6): 775-787 DOI: 10.1016/j.devcel.2011.04.018
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