Naturalists have been baffled for generations as to what might possibly be
the head of a sea star, often known as a "starfish." It is obvious which end
of a worm or fish is the head and which is the tail while observing them.
But it's been anyone's guess as to how to distinguish the front end of the
creature from the back thanks to their five similar limbs, any of which can
take the lead in moving sea stars over the bottom. Many have come to the
conclusion that sea stars may not even have a head because of their peculiar
body structure.
However, a recent study by the Chan Zuckerberg Biohub San Francisco
Investigators-led labs at Stanford University and UC Berkeley indicates that
the reality is very nearly the complete opposite. To put it briefly, the
scientists found gene signatures linked to head development almost
everywhere in young sea stars, while the expression of genes coding for the
body and tail regions of the animal was mostly absent.
A range of advanced molecular and genomic approaches were employed by
researchers to determine the locations of gene expression during the growth
and development of sea stars. Using micro-CT scanning, a Southampton team
was able to get previously unheard-of levels of detail regarding the
animal's shape and structure.
Another unexpected discovery was the localization of chemical signatures
normally associated with the front part of the head to the center of each
arm of the sea star. As one moves out towards the margins of the arms, these
signals become increasingly more posterior.
According to the research, which was published in Nature on
November 1st, sea stars are not headless; rather, they lost their bodies during the
course of evolution and now just have heads.
Lead author of the new study and postdoctoral fellow Laurent Formery
stated, "It's as if the sea star is completely missing a trunk, and is best
described as just a head crawling along the seafloor." "It's not at all what
scientists have assumed about these animals."
Daniel Rokhsar of UC Berkeley, an authority on the molecular evolution of
animal species, and Christopher Lowe, a marine and developmental biologist
from Stanford University, are two of the three co-senior authors of the
paper. They have been working together for ten years.
An astrophysical conundrum
Bilateral symmetry refers to the ability of almost all creatures, including
humans, to be divided into two mirrored halves along a single axis that runs
from their head to their tail. Three scientists were granted the 1995 Nobel
Prize in Physiology or Medicine for their work using fruit flies to show
that a set of molecular switches expressed in specific head and trunk
regions coded by genes are responsible for the bilateral, head-to-tail body
plan seen in most animals.
Since then, scientists have shown that the great majority of animal
species, including numerous invertebrates like worms and insects and
vertebrates like humans and fish, have this similar genetic
programming.
However, scientists' understanding of animal evolution has long been
confused by the structure of sea stars' bodies. Adult sea stars—and allied
echinoderms, such sea urchins and sea cucumbers—have a five-fold axis of
symmetry without a distinct head or tail in place of bilateral symmetry.
Furthermore, the mechanism underlying this peculiar five-fold symmetry in
genetic programming has remained a mystery.
The head-to-tail axis of sea stars may, according to some scientists, go
from the armored back of the creature to its tube-footed underside. Some
have proposed that the five arms of the sea star are copies of a typical
head-to-tail axis.
However, techniques for measuring gene expression, mostly established in a
small number of model species like mice and flies, do not function well in
the tissue of newborn sea stars, which has hampered efforts to firmly prove
such predictions. For an extended while, Lowe and his associates had a
strong desire to utilize genetic data to address the inquiry by charting
genetic activity throughout growing sea stars. However, such an extensive
examination proved intimidating given the absence of the sophisticated
genetic toolkits that have been established over decades of research and
exist for typical model species.
Revolutionary technology
At one of the quarterly Biohub Investigators meetings in San Francisco,
Lowe came upon a solution to this issue. A fellow researcher recommended
that he get in touch with PacBio, a Silicon Valley-based business that
manufactures genome-sequencing equipment. PacBio had spent the preceding
five years honing a method for sequencing vast amounts of genetic
information using postage stamp-sized chips that were crammed with millions
of separate chemical reactors, each poised to read lengthy sections of
acquired DNA concurrently.
HiFi sequencing, a method developed by PacBio, is a faster and less
expensive alternative to standard sequencing, which involves breaking up
genetic material into tiny bits in order to achieve precision. This method
yields extremely accurate data from intact, gene-sized DNA strands. It was
just what Lowe and his colleagues needed to start from scratch and build a
procedure for researching sea star genetics.
Former PacBio Scientific Fellow and co-senior author David Rank added, "The
kind of sequencing that would have taken months can now be done in a matter
of hours, and it's hundreds of times cheaper than just five years ago."
"These advances meant we could start essentially from scratch in an organism
that's not typically studied in the lab and put together the kind of
detailed study that would have been impossible 10 years ago."
With the use of this technology, the researchers were able to sequence the
sea stars' genomes and use a technique known as spatial transcriptomics to
identify the specific sea star genes that are active within the creature.
The researchers looked at changes in gene expression in three distinct ways
throughout the body of the sea star: from its center to the tips of its
arms, from its top to its underside, and from one side edge of its arms to
the other, in an attempt to find patterns that would suggest a head-to-tail
axis.
They then tagged each important gene individually with fluorescent dyes to
produce a precise map of their distribution inside the sea star body,
allowing researchers to gain a deeper understanding of how these genes
functioned.
The two most well-known theories on the body plan structure of sea stars
were proven to be false by the researchers. Rather, they observed that the
midline of the arms of sea stars had gene expression equivalent to the human
forebrain and other bilaterally symmetrical animals, whereas the outside
borders of the arms carried genetic expression comparable to the human
midbrain.
Only one of the genes normally associated with the animal trunk was
expressed in the sea star, and that too only at the extremities of its arms.
In humans and other bilaterians, the genes designating distinct subregions
of the head were expressed.
Formery stated that some odd-looking sea star ancestors preserved in the
fossil record do appear to have had a trunk. "These results suggest that the
echinoderms, and sea stars in particular, have the most dramatic example of
decoupling of the head and the trunk regions that we are aware of today,"
Formery said. "It just opens a ton of new questions that we can now start to
explore."
A gateway to fresh discoveries
Subsequent research goals for the team include determining if the genetic
patterning observed in sea stars is also present in sea urchins and sea
cucumbers. Formery, for his part, is interested in learning more about the
sea star's potential to tell us about the development of the nervous system,
which he claims is still little understood among echinoderms.
The researchers said that understanding more about the sea star and its
cousins may spur advances in medicine in addition to aiding in the
resolution of important questions about animal evolution. With hundreds of
tube feet, sea stars walk on flowing water as their stomachs protrude
outside of their bodies to digest their food. It makes sense that these
strange animals would have developed totally unanticipated means of
maintaining their health. If we took the time to learn about these methods,
we might be able to improve our methods for treating human illness.
"It's certainly harder to work in organisms that are less frequently
studied," Rokhsar stated. "But if we take the opportunity to explore unusual
animals that are operating in unusual ways, that means we are broadening our
perspective of biology, which is eventually going to help us solve both
ecological and biomedical problems."
