Timing is not only ticking
Many animals exhibit segmentation in development. A classic example being the sequenced formation of the backbone, linked to the ticking of a “segmentation clock” in the embryo. Max Planck researchers now discover the sound pattern known as the Doppler effect influences all segmentation
in the embryo.
Until now, segmentation patterning was thought to be determined simply by the time scale of genetic oscillations periodically triggering new segment formation. However, Max Planck researchers suggest a second influence over control of segmentation timing. Their findings show that the rhythm of segmentation is influenced by a Doppler effect from waves of proteins released by genes in both the head and tail of the embryo.
Their potentially revolutionary picture of the process of developmental segmentation is controlled not only by the time scale of genetic oscillations, but also by changes in oscillation profile and by tissue shortening.
Waves of oscillating gene expression are visible in pseudo-colors sweeping from the posterior to the anterior of the unsegmented zebrafish. The anterior end of this unsegmented tissue moves steadily into these on-coming waves, creating a Doppler effect that contributes to the rhythm of segmentation.
What do you, I and many other animals have in common? Perhaps it isn’t the first thing you think of, but we all have a distinctly segmented body. During our development, various cues integrate to form a specific number of embryo segments that give rise to ribs and vertebrae. The rhythm of this patterning process is crucial to forming the correct number and size of segments, but how is its timing actually controlled?
In vertebrates, the beginning and ending of gene expression waves are thought to be controlled by a complex genetic network – called the “segmentation clock”. Each stopped wave triggers the formation of a new segment. The underlying mechanism was thought to operate like a conventional clock that ticks precisely: one tick equals one new segment.
To examine this idea a team of biologists and physicists developed a new transgenic zebrafish (they named it Looping). Then they developed a multidimensional time-lapse microscope so that the could see and count waves of gene expressed proteins as well as segment formation — all at the same time. To their surprise they found that the beginning and end of waves happened at different frequencies. This meant that the timing of segmentation cannot be explained by one clock alone.They also saw that this difference in frequency was similar to the classic Doppler effect.
Travelling tissue and oscillating genes
Imagine an ambulance driving down the street. Did you ever notice how the pitch of the siren changes as it drives past? This is the Doppler effect. It is caused by changes in the frequency of the sound waves as the source comes towards an observer (you) and then drives away. The same thing would happen if you rapidly approached and then passed a stationary sound source. For example, if you jogged past someone sitting on a bench listening to music, that music would become louder as you approached the bench, but fade the further you jogged away.
It turns out that sound waves are not unlike gene expression waves. Gene expression waves travel from the posterior (from the tip of the tail) towards the anterior (the head) of the animal. As they travel, the embryo is developing, changing shape and tissue type as the waves shorten in duration.
There is also motion from the head end of the embryo, where new segments form, towards the tail known as the Dynamic Wavelength effect. These two "effects" or waves — Dynamic Wavelength and the Doppler — have opposing influences on the timing of embryo segmentation. But the Doppler effect is stronger, and determines the number and size of the developing ribs and vertebrae.
The findings could potentially revolutionise our concept of timing during development. The biological mechanism behind the change in the wave profile is still unclear, but it highlights the complex nature of embryonic development — and our need to expand our view of all of its complexity.
The research is published in the journal Science.
The team was guided by Andy Oates and Frank Jülicher from the Max Planck Institute of Molecular Cell Biology and Genetics together with colleagues from the Max Planck Institute for the Physics of Complex Systems in Dresden.
During embryonic development, temporal and spatial cues are coordinated to generate a segmented body axis. In sequentially segmenting animals, the rhythm of segmentation is reported to be controlled by the time scale of genetic oscillations that periodically trigger new segment formation. However, we present real-time measurements of genetic oscillations in zebrafish embryos showing that their time scale is not sufficient to explain the temporal period of segmentation. A second time scale, the rate of tissue shortening, contributes to the period of segmentation through a Doppler effect. This contribution is modulated by a gradual change in the oscillation profile across the tissue. We conclude that the rhythm of segmentation is an emergent property controlled by the time scale of genetic oscillations, the change of oscillation profile, and tissue shortening.
The Max Planck Society is Germany's most successful research organization. Since its establishment in 1948, no fewer than 17 Nobel laureates have emerged from the ranks of its scientists, putting it on a par with the best and most prestigious research institutions worldwide. The more than 15,000 publications each year in internationally renowned scientific journals are proof of the outstanding research work conducted at Max Planck Institutes – and many of those articles are among the most-cited publications in the relevant field.
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