A Salk Institute team of biologists, mathematicians, and physicists has uncovered a novel paradigm for cell communication that provides new insights into the complex question of how the body determines where organs are placed. The study focused on a fundamental question: how the body tells left from right. Although humans look fairly symmetric on the outside, their inner organs are placed quite asymmetrically; for example, the heart points to the left and the liver lies to the right side. "We know that in the phase of development, there is a genetic cascade that leads to the proper placement of organs. If that cascade is disrupted, the results can lead to major problems or be fatal," said Salk Professor Juan Carlos Izpisúa Belmonte, who published the findings in the January 8 issue of Nature. Still, scientists did not have a clear understanding of what triggers the genetic cascade that defines organ placement. Izpisúa Belmonte's group focused on the activity of the Notch pathway, an important player during embryo development and also during tumorigenesis, and a key factor for proper left-right asymmetry, as the same group and others had learned earlier this year.

"We knew that Notch activity was necessary for the normal, left-sided expression, but we were clueless as to what was activating Notch preferentially on the left side," said Angel Raya, lead author of the paper. "We examined several factors known to participate early in the establishment of the left-right axis, but none was responsible for what we were seeing."


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