Research has shown that the wrists and fingers of tetrapods
like the mouse at left are "the cellular and genetic
equivalents" of the fin rays in fish.
Scientists believe that many millions of years ago, our
aquatic ancestors made the leap from inhabiting the oceans
to living on dry land, marking the evolution of the first
four-limbed vertebrates known as tetrapods. Although the
tetrapods that inhabit the Earth today – including humans –
possess fragments of this aquatic past deep in the genetics
that make up their bodies, researchers are still struggling
to determine how fish developed limbs in the first place.
Now, a new study by University of Chicago researchers
furthers our understanding of this evolution by shedding
light on the relationship between fish fins and fingers.
One of the biggest sources of confusion in this area of
research lies in the fact that fin rays form from connective
tissue, while the fingers and toes observed in tetrapods
stem from cartilage. Their dissimilar nature led many
scientists to dismiss the possibility that fish fins were
related to fingers and toes and focus elsewhere for the
answer to this evolutionary riddle.
Neil Shubin, a professor at the University of Chicago and
senior author of the study, spent three years of
experimentation to force a rethink to this notion. Using
genetic editing and mapping techniques, Shubin and his team
were able to track fish cells as they developed, revealing
that the tiny bones on the ends of their fins are
genetically related to the fingers and toes that allow for
life on land.
Shubin's team used the CRISPR/Cas9 gene-editing technique
to delete specific genes in the zebrafish genome known to
play a role in limb development and then subsequently
crossbred numerous fish with these genetic deletions.
Meanwhile, lab member Andrew Gehrke worked on refining fate
mapping, the cell-labeling technique that would allow the
team to pinpoint the movement of specific embryonic cells in
the fish as they developed.
Using fate mapping, the team focused on the Hox genes,
which are known to play a big role in limb development.
Previous research has shown that the deletion of HoxD and
HoxA genes halts the development of wrists and digits in
mice, and in the current experiment, the team discovered
that the deletion of these same genes led to a reduction in
the long fin rays of the zebrafish.
"It was one of those eureka moments," says Gehrke. "We
found that the cells that mark the wrists and fingers of
mice and people were exclusively in the fin rays of fish."
In addition, the team used a high-energy computerized
tomography (CT) scanner to get a close look at the smallest
structures lurking within the fins of adult zebrafish,
structures that standard microscopes can't pick up.
The observations from the study suggest that the wrists
and digits of tetrapods stem from the same cluster of cells
as fish fins, supporting the idea that the hands and fingers
that we use today are the equivalent of the fins that
ancient fish used to traverse the oceans before they crawled
onto the terrestrial landscape.
Future research will further examine the Hox genes to
determine why these cell clusters lead to such different
structures in fish and humans and continue to study fossils
of the
Tiktaalik, a 375-million-year-old fish that developed
strong hind limbs despite the fact that it did not live on
land.
The findings were published in the journal
Nature.
Source:
University of Chicago