One-eyed sheep – basic research

By Rossana Soletti

A strange case helps us answer why we have two eyes

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The children’s book We Are All Extraordinary, by the North American RJ Palacio, tells the story of a little boy with one eye who lives like an ordinary boy but has puzzled looks and pointed fingers. He knows he can’t change his face, but he believes that people can change the way they see him. After reading, my seven-year-old daughter asked me, “If the boy is exceptional and we are all exceptional, why are we born with two eyes?”

The question may be simple, but the answer is a bit complex. I told her a different story first.

In the 1950s, people were surprised by the birth of one-eyed sheep on a farm in the interior of the United States. The secret of the Cyclops ewes caught both attention and much speculation, especially after other similar litters emerged on neighboring farms. Scientists from the Ministry of Agriculture were called in to solve this riddle, but no one suspected that it would take so many years of research.

The first hypothesis was that a genetic disease caused the changes, but after a series of crosses in the laboratory nothing happened: all sheep were born with two eyes and the typical face of the species. The researchers then observed that the birth of Cyclops ewes followed a seasonal pattern and was not limited to just flocks that grazed at high altitudes.

There the hypothesis arose that an environmental factor could affect the pregnancy of these animals. The identification of this factor did not come about overnight, of course. About ten years and many analyzes later, the answer finally came: the sheep consumed a herbaceous plant native to the region that caused deformities in the head of the fetus when ingested in the first few weeks of pregnancy.

There the riddle was solved: just remove the plant from the pastures and no more Cyclops sheep would be born. But just like children, scientists always want to know why: why did consuming this plant cause the birth of one-eyed sheep? There was still a few years of research until the chemical components of the plant were isolated and characterized with the identification of the culprit cyclopamine.

And it only took three decades to solve the other piece of the puzzle and put things right: the researchers observed that for the brain, eyes, and other structures of the face of animals (including humans) to develop properly, the cells of the embryo must Get information at the right time about proteins that act as signal conductors on a path called hedgehog or Hh. If the embryo is much smaller than a grain of rice, the Hh signaling pathways act on the cells in the center of the face, directing the instruction to migrate laterally, multiply and create two fields of view. When this path is blocked, multiple brain and facial malformations such as: B. Cyclopia. And who can block the Hh route? Eureka, it’s cyclopamine!

So many decades of research and discovery have brought us understanding beyond the processes necessary to form the eyes and faces of sheep, rats, or humans. Once we understand how cells communicate, we can also think about treatments to readjust cells with signal errors. Today we know that the Hh pathway may be overactivated in some tumor cells and therefore inhibitors of this pathway, similar to cyclopamine, are already used in the treatment of one type of skin cancer and are being tested for several other types of cancer …

Just like in the fiction of the boy who shows us the beauty of diversity with just one eye, the construction of scientific knowledge can lead us on extraordinary paths.

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Rossana Soletti is a professor at UFRGS Litoral, working primarily in the areas of oncobiology, morphology and scientific dissemination.

We know that children ask the best questions, and that science can have great answers for them. Each month, the Children’s Questions, Answers from Science series invites a scientist to answer one of these fundamental questions. Do you have a suggestion for a question or an agenda for the blog? Here’s how you can work together.

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