Written by
Catherine Zandonella, Office of the Dean for Research
April 20, 2019

The first moments of life unfold with incredible precision. Now, using mathematical tools and the help of fruit flies, researchers at Princeton have uncovered new findings about the mechanisms behind this precision.

In a new study published in the journal Cell, the team showed that cells determine exactly where they need to be and therefore what body parts they will become by optimizing the use of all information available from the genetic code. This optimization allows each cell to position itself within one cell’s width of where it should be, rather than making errors that later are corrected.

The study also demonstrates that a complex biological system can operate according to a mathematically optimal process. The team was able to predict the placement of cells to within 1 percent of their actual locations along the length of the embryo, showing that biological behaviors can be computed and predicted from theoretical principles.

“The information required to specify precise cell locations — and therefore what body parts they will become — is present and utilized at the earliest stages of development in fruit flies,” said Thomas Gregor, associate professor of physics and the Lewis-Sigler Institute for Integrative Genomics. “This contrasts with the prevailing view that the position of the cells is refined slowly over time.”

“The theoretical idea is very simple, which is that every cell is using all the information that it can squeeze out of the relevant genes,” said William Bialek, the John Archibald Wheeler/Battelle Professor in Physics and the Lewis-Sigler Institute for Integrative Genomics. “Something we’ve known for a while, but never stop being amazed by, is that the whole system is incredibly precise, and this fact is what spurred us to believe that the cells are using all the information that they can.”

Cells take cues from genes, or more specifically, from the protein molecules that those genes produce. But do the cells use all of the information to get everything right the first time? Or is the system messy, with mistakes that are repaired before irreparable harm is done to the embryo?

The question was exactly the type of big-picture problem that the team of biologists and physicists, who have been working together since the early 2000s, likes to tackle.

Thanks to previous work by team member Eric Wieschaus, the Squibb Professor in Molecular Biology and professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics, scientists know exactly which genes and molecules are involved in creating stripes across the embryo that mark the segments of the fly larva. If anything goes wrong, the stripes form in the wrong places or not at all.