Dartmouth scientists say they have figured out the chain of events that causes cell division to stop at the right time. The team tackled the problem in reverse by focusing on large cells that reduce their size through division until enough cells are formed to move to other stages of development.
"The early embryo is an ideal place to study cell size control," said Amanda Amodeo, lead researcher on the paper published in Current Biology recently. "The cells we work with are eggs that are visible to the eye. They don't need to grow before dividing, so it allows us to look at connections that are obscured in adult cells."
According to the study, a set amount of the protein histone H3 is loaded into an embryo before fertilization and is used up as the embryo divides into more cells. As histones are consumed to accommodate the growing number of nuclei, they release the enzyme Chk1 to bind with another protein, CDC25, to stop the multiplication of cells.
The mechanism is relatively straightforward: With histone H3 out of the way in a growing cell, the stop enzyme Chk1 finds and disables the protein that triggers cell cycle progression, CDC25.
"The key to our research result was coming up with the possibility that unusually large amounts of histone H3 may feed into the stop enzyme," said Yuki Shindo, first author of the paper. "Once we noticed that, we were able to test this idea in our living test tube, fruit fly eggs."
The new research builds on earlier studies which found that a biological constant exists between the size of a genome and the size of a cell. Researchers knew that once a balance point was achieved, cells would stop duplicating, but didn't understand how cells could determine the ratio.
Since the same molecules that control cell division—histone H3, CDC25 and Chk1—are all identified in cancer and other ailments, the finding can help researchers that are seeking answers to questions related to development and disease.