Mutant zebrafish reveals a turning point in spine's evolution
Single-letter change in DNA also makes the fish a useful model for human spinal defects

Date:
July 20, 2020
Source:
Duke University
Summary:
A chance mutation that led to spinal defects in a zebrafish has
opened a little window into our own fishy past. The single-letter
mutation showed that both the ancient and modern recipes for spine
development are still to be found in the fish genome.



FULL STORY ==========================================================================
A chance mutation that led to spinal defects in a zebrafish has opened
a little window into our own fishy past.


========================================================================== Rising fifth-year Duke graduate student Brianna Peskin, who started the
project during her first-year rotation in Michel Bagnat's cell biology
lab and "kinda kept coming back to it," was merely trying to figure out
why this one mutation led to developmental issues in a zebrafish's spine.

What she found is that embryos of the mutant fish have a single-letter
change in their DNA that alters the way they build the bones and other structures that make up their spine, leaving them with a shorter body and
a tortured looking spine that contains clefts dividing their vertebrae
in half.

The mutant fish are named spondo, short for spondylos which is Greek
for spine, and also a reference to dispondyly, a condition where each
vertebra has two bony arches not one.

But that's not the end of the story.

When Bagnat's research colleague Matthew Harris of Harvard Medical School showed some pictures of the mutant fish spine to a colleague in fish paleontology, Gloria Arratia at the University of Kansas, she immediately spotted that the mutants look a lot like fossil specimens of ancestral
fish whose style of spine has gone out of fashion in most living fishes.



==========================================================================
"And then they both got really excited because they were noticing
these similarities between ancestral fossil specimens and our mutant,"
Peskin said.

The tiny mutation showed that both recipes for spine development are
still to be found in the fish genome.

In the bony fish, known as teleosts, building the spine relies on a
tube-like structure running the length of the developing embryo called the notochord. The notochord sets up the patterns that lead to articulated
bones and cartilage in the developing spine by sending chemical signals
that attract different molecules and cell types to different regions --
bone parts here, cartilage parts there.

Human embryos start with a notochord too, but it doesn't pattern the
bony vertebrae the way it does in teleosts; it ends up building the
cartilage pucks between the bones, the intervertebral discs.

The gene that is mutated in spondo fish is unique to teleosts and the
mutant fish's notochord doesn't set up the patterning the way it does
in other fish.

Rather, its patterning reverts to an ancestral form. So, this tiny
difference in DNA may be where land animals like us parted company with
our fish ancestors a very, very, very long time ago.



========================================================================== While the zebrafish (Danio rerio) has become a laboratory workhorse for
all sorts of interesting studies, its usefulness as a model of human
spine development has been in doubt because they grow their backbones differently.

But not anymore. The research team's new paper, which appears July 20 in Current Biology, shows that the difference between the way teleosts and
land animals grow their spines comes down to signaling from the notochord, which was revealed by this single-letter change in the DNA.

And that, in turn, gives them the insight to study human spinal defects
with these fast-growing, translucent fish, because the spondo mutants
are sensitive to factors known to cause congenital scoliosis in human
children, a curvature of the spine.

"This work not only gave us a glimpse into spine evolution, but also made
us understand how the spine is put together in mammals," said Bagnat,
who is an associate professor of Cell Biology in the Duke School of
Medicine. "Moving forward, we'll be able to use mutations like spondo to unravel the complex genetics of scoliosis and other spine defects that
are rooted in the biology of the notochord and have been intractable until now." "Overall, what this study means is that notochord signals are key
to establishing the spine. These signals have changed over evolutionary
time and account for differences that exist in spine patterning strategies across vertebrates," Peskin said. "So we are all fish after all."

========================================================================== Story Source: Materials provided by Duke_University. Original written
by Karl Leif Bates.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Brianna Peskin, Katrin Henke, Nicola's Cumplido, Stephen Treaster,
Matthew P. Harris, Michel Bagnat, Gloria Arratia. Notochordal
Signals Establish Phylogenetic Identity of the Teleost
Spine. Current Biology, 2020; 30 (14): 2805 DOI:
10.1016/j.cub.2020.05.037 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200720145915.htm

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