‘Domino of life’ discovered

Researchers at the Yale School of Medicine have discovered what they believe are the mechanisms that help jumpstart life.

Through studying the early development of zebrafish, professor of genetics Antonio J. Giraldez and his team uncovered three proteins that transition a fertilized egg from reading the genetic code of the mother to reading its own. The findings may help researchers further understand stem cell development, Giraldez said. The study was published in the journal Nature on Sept. 22.

“You can think about it as molecular puberty,” said Giraldez. “The embryo becomes independent of the mother and starts taking charge of its own development.”

Previously, scientists were unsure of exactly how embryos gained independence from maternal DNA. While scientists knew that one of the first genes activated was the “molecular scissor” that made embryos independent, they were unclear which other factors were involved. To discover the key genes for initiating life, the researchers blocked certain genes to see which disruption would prevent the embryo from developing. When the geneticists blocked the genetic pathway of ­the Nanog, Oct4 amd SoxB1 from entering the cell, they found that the embryo was unable to read its own genetic instructions and stayed in an immature state forever ­— illuminating which proteins were instrumental in kickstarting the development of the embryo.

The researchers explored this question using zebrafish because they lay hundreds of eggs which are easy to study during development, said coauthor and postdoctoral fellow Miler T. Lee.

“The fish are much easier to study than humans,” Lee said. “A lot of the questions we’re exploring are fundamental to all animals.”

Giraldez said scientists have been interested in finding this so-called “domino of life” for at least as long as his seven-year tenure at the School of Medicine. While the finding clarifies the earliest stages of life, Giraldez said he did not feel the ethical implications were significant.

Coauthor and third-year medical student Ashley Bonneau Bonnea said despite the finding, there is still much to be discovered about the mechanisms that take an embryo from a single cell to a fully functional organism.

“Now we know what pushes the domino,” said Bonneau. “But what puts the finger in place, we don’t know. We have to understand what actually allows that to occur.”

The research was supported by the National Institutes of Health, the Pew Program in Biomedical Sciences, and the Yale Scholars Program.

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