How Do Embryos Know How Fast to Develop?

Different species live their lives at remarkably different paces. This biological tempo is apparent even before birth: In just three weeks, a fertilized egg can turn into a baby mouse, whereas in elephants, this process can take up to 22 months. While these different trajectories have long been appreciated, the biological mechanisms that set the pace during development remain incompletely understood.

Body size does play a role, but it’s not the only important factor. In fact, the pace of embryogenesis—the period of development during which most of the internal organs form—doesn’t scale with body weight.¹ For example, in cattle, this phase lasts about 40 days, but in the comparatively diminutive marmoset, it is closer to 80 days.

Miki Ebisuya, a developmental biologist at the Dresden University of Technology, has long been interested in how biological timekeeping varies across species. During the course of this research, she has explored how the length of embryogenesis scales with the period of the segmentation clock—oscillations in patterns of gene expression that help drive the formation of the backbone and other body segments.

The core segmentation clock gene, called hairy and enhancer of split 7 (HES7), is a transcription repressor, explained Ebisuya. “If HES7 protein is expressed, it starts repressing its own expression, and therefore the HES7 protein level goes down,” she said. “Then the repression is released, and the expression level goes back up. It's a one-factor negative feedback loop.” Using a stem cell-derived model so that temperature and other extracellular factors could be controlled, Ebisuya found that the period of this genetic clock was species-specific. For instance, it was 122 minutes in mice, 236 in a rhinoceros, and 388 in a marmoset.

But what controls the pace of the segmentation clock? The answer is complicated. The HES7 feedback loop—and thus the periodicity of the clock—is governed by the speed of multiple biochemical processes, including transcription, translation, intron removal, and mRNA and protein degradation.² Ebisuya wanted to investigate cellular metabolism as a potential modulator of species-specific tempo. “But the problem with metabolism is that the definition is not so clear,” she said. Indeed, her recent paper suggested pharmacologic inhibition of different metabolic processes had distinct effects on the kinetics of different sections of the HES7 feedback loop.³

“My current working hypothesis,” said Ebisuya, “is that rather than a single, common global modulator of species-specific tempo, each species combines different metabolic modulators to achieve its own tempo.”