A group of scientists from Barcelona and Kyoto has found that the signal of the segmentation clock, which is responsible for the formation of body segments, beats more slowly in humans than in mice.
The difference is caused by certain biochemical reactions progressing in human cells at a lower rate. The research will give scientists insight into how the human body develops and might help to fight certain developmental diseases.
A scientific mystery
The rhythmic signal of the segmentation clock is a genetic network that governs the sequential formation of the body pattern in embryos.
In mice, an oscillation of the segmentation clock occurs approximately once every two hours. In human cells, an oscillation occurs approximately once every five hours. The reason for the difference has remained a mystery to the scientific community.
In order to crack this puzzle, a group of researchers from the RIKEN Center for Biosystems Dynamics Research, EMBL Barcelona, Universitat Pompeu Fabra, and Kyoto University transformed mouse embryonic stem cells and human induced pluripotent stem (iPS) cells into a cell type known as presomitic mesoderm (PSM).
They made this change because the development of the presomitic mesoderm is governed by the segmentation clock.
The researchers ran tests to discover whether the difference in oscillation frequency between the two cell types was due to the ways that multiple cells communicate with each other, or was instead due to differences in the biochemical processes within each individual cell.
Swapping genes between human and mouse cells
By running experiments that either isolated cells or blocked important signals, the team of researchers found out that the difference was a result of the biochemical processes within individual cells.
The team then swapped the HES7 genes, which plays a key role in the oscillation cycle in both mice and humans, between human cells and mouse cells. In doing so, they found that both the human and the mouse version of the HES7 protein were degraded much more slowly in human cells than in mouse cells.
What's more, the research team found that the time it took cells to transcribe the HES7 gene into messenger RNA (mRNA), to process the mRNA molecule, as well as to translate it into proteins was also very different for both sets of cells.
"We could thus show that it was indeed the cellular environment in human and mouse cells that made the difference in the biochemical reaction speeds, and thus in the time scales involved," Ebisuya, corresponding author Miki Ebisuya, Group Leader at EMBL Barcelona, who performed the work at RIKEN BDR and at EMBL, explained in a press release.
"Our study will help us to understand the complicated process through which vertebrates develop," says Ebisuya.