Insight: Cellular clocks help explain why elephants are bigger than mice

These cellular clocks help explain why elephants are bigger than mice

In her laboratory in Barcelona, Spain, Miki Ebisuya has built a clock without cogs, springs or numbers. This clock doesn’t tick. It is made of genes and proteins, and it keeps time in a layer of cells that Ebisuya’s team has grown in its lab.

Biologists are uncovering how tiny timekeepers in our cells might govern body size, lifespan and ageing.

A wave of research is starting to yield answers for one of the many clocks that control the workings of cells. There is a clock in early embryos that beats out a regular rhythm by activating and deactivating genes. This ‘segmentation clock’ creates repeating body segments such as the vertebrae in our spines. This is the timepiece that Ebisuya has made in her lab.

“I’m interested in biological time,” says Ebisuya, a developmental biologist at the European Molecular Biology Laboratory Barcelona. “But lifespan or gestation period, they are too long for me to study.” The swift speed of the segmentation clock makes it an ideal model system, she says.

Biologists have been studying the segmentation clock since the 1990s, and they know that it runs about twice as fast in mouse embryos as it does in human embryos. The speed at which an embryo develops, or at which different parts of it develop, has an important influence on the adult body. Ebisuya and others want to understand how differences in developmental pace give rise to organisms with such different bodies and behaviours.

In the past three years, answers have begun to emerge. This is mostly because biologists can now grow the tissue that generates the segmentation clock in vitro, from human stem cells, and observe its activity in detail.

“What’s truly exciting here is that you can watch it in human [tissue],” says stem-cell biologist Helen Blau at Stanford University in California. “It’s a major advance.”

The findings are already overturning some long-held assumptions about how different animals develop. So far, there is no sign of a master gene controlling the speed of the segmentation clock. Instead, its speed seems to be controlled by the differing rates at which proteins are broken down. Scientists had assumed the speed was mostly constant for each protein across animals, so the discovery might require them to revise some molecular-biology textbooks.

These differences in cellular speed might even help to explain unique features of human development, such as our oversized brains, protracted childhoods and long lives, relative to many other species.

If results from studies of the segmentation clock are true, this tiny, fleeting timepiece could help to reveal the existence of deeper, biochemical principles that shape all our lives.

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