Long presumed to have no heads at all, starfish may be nothing but

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."