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.