What mechanism generates our fingers and toes?

December 14, 2012

Montréal, December 14, 2012 - Dr. Marie Kmita and her research team at the IRCM contributed to a multidisciplinary research project that identified the mechanism responsible for generating our fingers and toes, and revealed the importance of gene regulation in the transition of fins to limbs during evolution. Their scientific breakthrough is published today in the prestigious scientific journal Science.

By combining genetic studies with mathematical modeling, the scientists provided experimental evidence supporting a theoretical model for pattern formation known as the Turing mechanism. In 1952, mathematician Alan Turing proposed mathematical equations for pattern formation, which describes how two uniformly-distributed substances, an activator and a repressor, trigger the formation of complex shapes and structures from initially-equivalent cells.

"The Turing model for pattern formation has long remained under debate, mostly due to the lack of experimental data supporting it," explains Dr. Rushikesh Sheth, postdoctoral fellow in Dr. Kmita's laboratory and co-first author of the study. "By studying the role of Hox genes during limb development, we were able to show, for the first time, that the patterning process that generates our fingers and toes relies on a Turing-like mechanism."

In humans, as in other mammals, the embryo's development is controlled, in part, by "architect" genes known as Hox genes. These genes are essential to the proper positioning of the body's architecture, and define the nature and function of cells that form organs and skeletal elements.

"Our genetic study suggested that Hox genes act as modulators of a Turing-like mechanism, which was further supported by mathematical tests performed by our collaborators, Dr. James Sharpe and his team," adds Dr. Marie Kmita, Director of the Genetics and Development research unit at the IRCM. "Moreover, we showed that drastically reducing the dose of Hox genes in mice transforms fingers into structures reminiscent of the extremities of fish fins. These findings further support the key role of Hox genes in the transition of fins to limbs during evolution, one of the most important anatomical innovations associated with the transition from aquatic to terrestrial life."
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About the research project

The study published in Science was a collaborative project between the teams supervised by Drs. Marie Kmita (IRCM), James Sharpe (CRG Barcelona, Spain) and Maria A. Ros (University of Cantabria, Spain). The research conducted at the IRCM was funded by the Canadian Institutes of Health Research and the Canada Research Chairs Program. The article's second first author Is Luciano Marcon from the European Molecular Biology Laboratory (EMBL) and the Pompeu Fabra University in Spain.

For more information on this scientific breakthrough, please refer to the article summary published online by Science: http://www.sciencemag.org/content/338/6113/1476.

About Dr. Marie Kmita

Marie Kmita obtained a PhD in cell and molecular biology from the Université de Reims in France. She is an Associate IRCM Research Professor and Director of the Genetics and Development research unit. Dr. Kmita is also Assistant Professor-Researcher in the Department of Medicine (accreditation in molecular biology) at the Université de Montréal, and Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) and the Department of Biology at McGill University. Dr. Kmita holds the Canada Research Chair in Molecular Embryology and Genetics. For more information, visit www.ircm.qc.ca/kmita.

About the IRCM

Founded in 1967, the Institut de recherches cliniques de Montréal (IRCM) (www.ircm.qc.ca) is currently comprised of 37 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.

About the Canadian Institutes of Health Research (CIHR)

CIHR is the Government of Canada's health research investment agency. CIHR's mission is to create new scientific knowledge and enable its translation into better health, more effective health services and products, and a stronger Canadian health care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 14,100 health researchers and trainees across Canada.

Institut de recherches cliniques de Montreal

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