Exploring the precision of embryonic development
Physicists and biologists collaborate to study the way cells use molecular information. Samantha Page reports.
How does the fruit fly get its stripes? Very specifically.
At least that’s the conclusion of physicists and biologists from Princeton University in the US, who found that during embryo formation fruit fly cells use “all information available from the genetic code” to position themselves within a single cell’s width of where they are supposed to be.
“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," says physicist William Bialek.
"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."
In a paper published in the journal Cell, the researchers report that using theoretical principles they were able to predict where cells will end up were accurate to within 1% of the ultimate locations.
Fruit flies form stripes between their segments during embryonic formation. Previous research shows that the stripes are formed according to the directions from the types of “signalling molecules,” which are passed on from fly mother to egg. The molecules activate special genes, known as gap genes, that create the gaps (and stripes) between fly segments.
Researchers used measurements of the expression of the gap genes and the molecules produced along the embryonic body to model how the cells find their places.
"One can imagine cells as GPS devices which, instead of satellite signals, collect molecular ones to figure out their locations. We are able to decode how such molecular signals specify positions along the length of the early fly embryo," says Mariela Petkova, who took the initial measurements.
Petkova also measured placement of cells in fruit fly larva that was genetically mutated, and it was there that the researchers found the most solid proof of their hypothesis. The mathematical predictions for cell placement work for the mutated genes.
"We used genetic manipulations to shuffle the gap gene patterns and 'trick' the cells into 'thinking' they were somewhere else along the length of the embryo," Petkova says. "We put these shuffled patterns through our decoder and built decoding maps, which told us where the cells were versus where they thought they were.
“Using these maps, we predicted where the embryos would make stripes. When we looked at these mutant embryos under a microscope, we actually found the stripes at the predicted locations! It was very satisfying."
The study builds on work by Eric Wieschaus, who earned the Nobel Prize in Physiology or Medicine in 1995. He and another researcher are credited with discovering gap genes.
Wieschaus is also a co-author of the new research, which he says is the first time that scientists have measured how much information cells use during development.
"The experiment defines the first truly quantitative measure of how much information cells have available for crucial developmental decisions and how much of that information they actually use," he says.
“This gives us an amazing tool for understanding how decision-making in biology actually works, one that is useful at levels ranging from the way proteins bind to DNA to how new biological pathways arise and compete during evolution.”