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Study fishes out new role for prostaglandins

ion.

Because they develop outside the mother and are transparent, zebrafish embryos provide a unique model in which to examine prostaglandin's role in development.

Yong Cha, a graduate student in DuBois' lab and first author on the study, established a collaboration with zebrafish researcher Solnica-Krezel to study this process.

The researchers inhibited the production of a specific type of prostaglandin, PGE2, in zebrafish embryos and examined their development.

In embryos treated with the inhibitor, gastrulation was arrested or slowed down significantly. The resulting embryo was also shorter than an untreated embryo.

"What is spectacular," said Solnica-Krezel, "is that…if you just put some prostaglandin back in the culture medium, you rescue the phenotype."

In another set of embryos, the researchers blocked prostaglandin receptors, EP2 and EP4. Blocking the EP4 receptor caused defects similar to those associated with blocking PGE2 synthesis. When the researchers analyzed cell movement, they found that the shapes and trajectories of embryonic cells were normal ?they simply moved much slower. This suggested that signaling through the EP4 receptor regulates the speed of cell movements during gastrulation.

The sluggish cell movements could have profound implications for development.

"Timing (in development) is really important," DuBois explains. "If you are traveling and have to get to the train station at a particular time, if you are too slow, you are going to miss the train. If you don't get on that part of the trip, that disturbs the whole agenda."

"Development synchronizes or orchestrates a myriad of events in the proper sequence (lots of trains)," said Solnica-Krezel, "and sometimes one train wreck can halt the entire process."

While 'bad timing' during development can spell the end for an embryo, finding ways to exploit this pathway could have beneficial effects in cancer cells
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Source:Vanderbilt University Medical Center


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