Researchers at the Francis Crick Institute have identified the clock that sets the speed of embryonic development. They have discovered that the mechanism is based upon protein stability.
Many animals share features in their organisation, such as body plan and organ systems. In addition, all mammals follow the same steps in development, from embryo to adult. This process involves the same series of events, in the same order, using similar genes and molecular signals. Nevertheless, the speed at which they progress differs considerably from one species to another. For example, mouse motor neurons take three days to develop, whereas in humans, they take over a week.
To gain further insight into the speed of development in different species, researchers at the Crick looked at motor neurons from humans and mice to identify molecular differences that would explain differences in pace. To do this, they grew motor neurons from stem cells in the lab, so that the cells developed without any influence from the embryo environment.
Different development timescales
The results, published in Science, revealed that human motor neurons took 2.5 times longer to develop than mouse motor neurons. As a result, the team proposed that the mechanism must be within the cells, not within the surrounding environment. The team also introduced human DNA sequences into mouse cells to check if genes were responsible. However, these did not impact speed of development either.
Instead, the data revealed that changes in protein stability correlated with development tempo. For example, slower temporal progression in humans corresponded with increased protein stability. They found that the faster rate of protein turnover in mouse cells accounted for the faster pace of motor neuron formation.
Teresa Rayon, researcher at the Francis Crick Institute, stated:
“Human and mouse motor neurons use the same genes and molecules for their embryonic development, it just takes longer for the process to play out in humans. Proteins are simply more stable in humans than mouse embryos and this slows the rate of human development.
It’s as if mouse and human embryos are reading the same musical score and playing the same tune but the metronome ticks more slowly in humans than in mice. Now that we’ve found the metronome, we want to understand how to change its speed.”
The identification and understanding of a molecular mechanism that explains embryonic development has implications for regenerative medicine and for the use of stem cells in understanding disease. The ability to speed up or slow down the development of stem cells could help refine methods for production of cell types for research and therapeutic applications. It may also provide important insight into slowing the growth of cells in diseases, like cancer.
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