A new study from EMBL Barcelona researchers shows that metabolic activities selectively modulate the segmentation clock, which varies depending on the species.
Embryonic development is a rigorously timed process. Many cellular activities must be synchronised to properly form tissues and organs. Although the molecular mechanisms of such development are similar across species, the speed at which these processes occur varies significantly. For example, it takes approximately 60 days from fertilisation to organ formation in humans, compared to just 15 days in mice.
Miki Ebisuya, Group Leader at EMBL Barcelona, now a professor at Physics of Life TU Dresden, and her group set out to determine whether metabolic activity serves as a global modulator of developmental tempo. Their findings revealed that contrary to a preexisting hypothesis in the field, metabolism does not serve as the overarching modulator for developmental speed across species. The study has been published in the journal Nature Communications .
For decades, scientists have disputed whether metabolism acts as a common global modulator, simultaneously regulating the tempo of many developmental processes. Recent studies suggest that metabolic activity can influence developmental timing. For instance, regulating cell metabolism can alter the tempo of developmental processes like the segmentation clock (oscillating genes that regulate the formation of body segments that give rise to the vertebrae and ribs) and neurogenesis (formation of new nerve cells). This has given rise to the hypothesis that metabolism is the ultimate global modulator controlling the tempo of all biological processes.
"Our work suggests that interspecies differences in developmental tempo cannot be attributed to a single principle, and instead result from the interplay of multiple principles," said Mitsuhiro Matsuda, Staff Member at TU Dresden and first author of the study.
Ebisuya and her group have been studying the segmentation clock for a long time. It consists of three key molecular processes: intron processing delay - the time taken to process mRNAs before protein synthesis, protein production, and degradation.
In the new study, the Ebisuya Group perturbed metabolism processes to examine their effects on the rhythm of the segmentation clock. They inhibited glycolysis, the pathway that breaks down glucose for energy, and observed that it slowed the degradation of a crucial protein called Hes7 and extended the time required for its production. However, this inhibition did not affect the intron processing delay. In contrast, inhibition of mitochondrial metabolism slowed down the intron processing delay without affecting protein degradation and production. In addition, they discovered that combining the two metabolic inhibitors enables the manipulation of all three processes at once.
The group has previously reported that the tempo of each molecular process within the segmentation clock exhibits scaling across animal species, i.e. the developmental speed was closely correlated with the rate of certain molecular processes in different animals.
"We now believe that these scalings were achieved through combinations of multiple selective modulators shaped by evolutionary constraints, rather than a single global modulator," said Ebisuya.
