University of Toronto researchers have discovered a key mechanism in tissue formation that could have implications for tissue engineering, as well as for diseases such as spina bifida and cancer.
U of T professor Rudolf Winklbauer and postdoctoral fellow Hiromasa Ninomiya, of the Department of Zoology, have found that the mechanism that controls cell differentiation is the same one that controls tissue elongation. The finding, published in the July 15 issue of Nature, provides insight into the intricacies of "morphogenesis", a crucial step in embryonic development through which cells and tissues form into different shapes. Deviations in this process can lead to birth defects.
"Morphogenesis has always fascinated scientists," says senior author Winklbauer. "It underlies much of embryonic development and is involved in pathological conditions such a spina bifida, a common birth defect where the spinal cord fails to develop properly."
Using tissue from frog embryos, Ninomiya and Winklbauer studied "convergent extension" (a process in which a tissue elongates as cells change their positions) and how it relates to cell differentiation. By administering different doses of activin, a protein known to induce cell differentiation, various cell types can be created such as those that form the tail (posterior cells) and those that form the head (antero cells) in the embryo. As Hiromasa and Winklbauer found out, even slight differences in activin doses yielded cells that behaved differently although they formed a single tissue. As these cells developed in vitro, they automatically grouped themselves at opposite ends to form the elongate dorsal tissue, which would later develop into the spine of the frog.
"It's not just that these cells differentiate but they remember where they're supposed to go," says Winklbauer. "Even when these cells are mixed together, they move automatically to the right place. By understanding this process, researchers will be better able to study the molecular basis of how tissues are shaped.
Until now, little has been known about how the overall direction of tissue shape change is controlled to ensure normal embryonic development. This finding could also have implications for tissue engineering, for researchers who might want to control the shape of a tissue or organ growing in vitro.
Winklbauer stresses that there is still much more work to be done to link the findings to formulating a cure for diseases. "Identifying this common mechanism is the first piece of the puzzle," he says. "We must now identify the molecules that allow this process to take place."
The study was funded in part an International Collaborative Grant from the Human Frontier Science Program Organization to Rick Elinson, co-author, formerly of U of T and now Duquesne University, Pittsburgh, and by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institute of Health Research, and the Canada Foundation for Innovation.
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