(PHOTO CREDIT: MCT CAMPUS)
Zebrafish embryos were used to illustrate the similarities between the pathways involved in the development of cancer and the development of embryos. (PHOTO CREDIT: TRIBUNE NEWS SERVICE)

Every other week, Ruchi Shah, a junior biology major, will take a look at Stony Brook-related science and research news.

The development of cancer and the development of an embryo seem to be two different processes, but researchers at Stony Brook University have found parallels between the pathways involved in both.

“A lot of the same developmental pathways used to create an embryo become reactivated in cancer, without the proper control that is present in embryogenesis,” Dr. Benjamin Martin, assistant professor of biochemistry and cell biology at Stony Brook University, said.

Martin’s research focuses on one of those pathways, known as Wnt signaling, which plays a critical role in a process called Epithelial to Mesenchymal Transition (EMT).

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Imagine that the epithelial cells are like bricks that are held tightly together. EMT is a process that transforms the bricks to more jelly-like mesenchymal cells that can leave their initial spot and travel.

In development, embryonic stem cells must undergo EMT to become mesoderm and eventually muscle and bone.

Likewise, a prevailing theory in cancer research is that cancer cells undergo EMT, allowing them to leave the area of the tumor, enter the bloodstream and metastasize to other areas of the body.

To better understand the role of Wnt signaling and EMT, Martin used zebrafish embryos to visualize how this pathway controls cellular behavior during development.

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The results shed light on the decision of embryonic cells to become either spinal cord cells or muscle cells, which could lead to more accurate regenerative medicine.

Zebrafish are an ideal model because they are multicellular and transparent, allowing scientists to visualize organ formation and cell movement as it happens in the living organism.

Martin said he and his team transplanted genetically altered cells that do not have Wnt signaling into normally developing embryos to “understand the mechanism by which the pathway controls the EMT process and the subsequent patterning of the embryo.”

The cells that did not have Wnt signaling could not undergo EMT, did not become mesoderm, and ended up in the spinal cord. Since the cells were fluorescently labeled, scientists could visualize the route of the cells to become a part of the spinal cord.

The cells without Wnt signaling also could not be rescued by neighboring cells that did have a normally functioning pathway. This means that the pathway is cell autonomous as only the mutant cells expressed the mutant phenotype.

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These results allow Martin to eliminate thousands of players that could not be involved in the pathway, thus making it easier to identify downstream targets.

A second aspect of Martin’s research focuses on the decision of mesoderm cells to become either blood vessel cells or muscle cells.

Normally, the tissue in the tail bud region of the zebrafish embryo is muscle with a few blood vessels. BMP is a pathway that is known for its role in mesoderm patterning.

To examine the role of BMP in the decision of mesoderm cells, Martin and his team used transgenic lines of zebrafish in which the BMP pathway can be activated or deactivated by placing the fish in warm water.

When BMP was inhibited, there were large blocks of muscle tissue where blood vessels should have formed, and when the BMP was activated, there was a big expansion of the blood vessels in regions that should have formed blood vessels. This means that BMP plays a critical role in instructing a cell to become a blood vessel.

Not only do these results have significance in terms of embryonic development, but they also increase understanding of cancer cells. The more blood vessels in a tumor, the more nutrients can reach the cancer cells, thus allowing them to survive and multiply.

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Martin’s lab is now beginning to examine how multiple signaling pathways like Wnt and BMP interact to better understand how they coordinate cell behavior and fate determination in developing embryos and cancer cells.

 

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