Scientists at the Francis Crick Institute and the Max Planck Institutes in Dresden, Germany have, for the first time, sped up a clock that controls development in zebrafish embryos – causing the embryos to develop more, smaller body segments than usual and to make these faster.
As well as providing important insights into embryonic development, this groundbreaking work has implications for understanding congenital scoliosis in humans. This is a condition that occurs during development in which the back bones are malformed and the spinal column is twisted. It can be painful and debilitating and severe cases can even lead to problems such increased pressure on the heart or lungs.
Andrew Oates of the Crick explained: “The body segments of all vertebrates (all animals with backbones, including humans) are generated during embryonic development. These segments are evident in humans as our segmented backbone. The segments are added one by one in a head-to-tail order during development, and this rhythmic and sequential addition is controlled by a biological clock that ticks in the tail end of the embryo.”
Previous researchers have been able to break this clock, producing defective segments, and to slow it, producing longer and fewer segments. But this is the first time anyone has been able to speed it up and keep it ticking.
Dr Oates’ team achieved this by genetically engineering the cells in the zebrafish segmentation clock to exchange synchronising signals at higher levels. Mutant zebrafish embryos that lack a signalling gene called DeltaD cannot synchronise their segmentation clock cells and develop scoliosis. The researchers generated transgenic zebrafish that expressed DeltaD with its normal pattern, but at much higher levels. They used time-lapse microscopy to watch the embryos and measure the speed at which new segments formed and examined the oscillating patterns of gene expression in the embryo to see how they had affected the clock.
The results revealed that the embryos expressing the most DeltaD had altered patterns of gene expression and made body segments faster. The resulting fish had more segments, which were all slightly smaller than usual.
Dr Oates said: “This shows that by tuning the speed of the clock, we can make animals with more or fewer body segments. It also shows the signals exchanged by the cells to synchronise their rhythms can also change the speed of the clock.
“This work has implications for understanding congenital scoliosis, which occurs when the cells of the segmentation clock do not oscillate in synchrony. By understanding how to control synchronisation better, we may one day be able to help the cells to talk to each other and prevent some forms of this condition.”
The paper, Faster embryonic segmentation through elevated Delta-Notch signalling, is published in Nature Communications.