For centuries, naturalists have wondered what might constitute the head of a starfish. When observing a worm or fish, it’s clear which end is the head and which is the tail. But with their five identical arms – any of which can independently propel the starfish along the seafloor – no one knew how to distinguish the front of the organism from the back. This unusual body structure led many to conclude that starfish perhaps don’t have heads at all.

But new research from Stanford University and University of California Berkeley, each led by researchers from the Chan Zuckerberg Biohub in San Francisco, has uncovered the truth may be closer to the opposite.

In summary, while the team detected genetic signatures associated with head development in nearly all juvenile starfish, expression of genes encoding the torso and tail sections of the animal were largely absent.

The unusual five-axis symmetry of starfish (Patiria miniata) has long confounded our understanding of animal evolution
The unusual five-axis symmetry of starfish (Patiria miniata) has long confounded our understanding of animal evolution | photo Laurent Formery

Another surprising finding is that molecular signatures typically associated with the frontal part of the head were located in the center of each of the starfish’s arms, and these signatures became progressively more posterior towards the arm edges.

The research, published in Nature, suggests that far from lacking a head, over time starfish lost their body to become solely heads. It’s as if the starfish is completely missing the trunk and is better described as a head crawling along the seafloor, explains Laurent Formery, a postdoctoral fellow funded by the Biohub and lead author of the new study. This is completely unlike what scientists have assumed about these animals.

Two of the study’s three leading co-authors, marine biologist and developmental biologist Christopher Lowe from Stanford University and Daniel Rokhsar from UC Berkeley, an expert in the molecular evolution of animal species, had been collaborating for a decade and were part of a team funded by CZ Biohub SF’s Intercampus Research Awards. Lowe cited the award, which funded a joint postdoctoral position between both laboratories for Formery, as an important catalyst for the new discovery.

Micro-CT scan of a starfish showing the skeleton (grey), digestive system (yellow), nervous system (blue), muscles (red) and aquatic vascular system (purple)
Micro-CT scan of a starfish showing the skeleton (grey), digestive system (yellow), nervous system (blue), muscles (red) and aquatic vascular system (purple) | photo University of Southampton

The work we set out to do together was very ambitious and the type of thing that usually doesn’t mesh well with traditional funding mechanisms, said Lowe. The Biohub’s willingness to take risks and support a joint position between our labs has been critical to the project’s success.

Nearly all animals, including humans, have bilateral symmetry, meaning they can be divided into two mirrored halves along a single axis running from head to tail. In 1995, three scientists were awarded the Nobel Prize in Physiology or Medicine for using fruit flies to demonstrate that the bilateral head-to-tail body plan seen in most animals arises from the action of a series of molecular switches, encoded by genes, that are expressed in defined regions of the head and trunk.

Since then, researchers have confirmed this same genetic programming is shared by the vast majority of animal species, including vertebrates like humans and fish, and many invertebrates like insects and worms. But the starfish’s body plan has long confused scientists in their understanding of animal evolution.

Micro-CT scan of a starfish showing the skeleton (grey), digestive system (yellow), nervous system (blue), muscles (red) and aquatic vascular system (purple)
Micro-CT scan of a starfish showing the skeleton (grey), digestive system (yellow), nervous system (blue), muscles (red) and aquatic vascular system (purple) | photo University of Southampton

Instead of showing bilateral symmetry, adult starfish – and other related echinoderms like sea urchins and sea cucumbers – have a fivefold radial symmetry with no clear head or tail. And no one has been able to determine how genetic programming drives this unusual fivefold symmetry.

Some scientists proposed the starfish’s head-tail axis might extend from its armored back to its foot-lined belly. Others suggested each of the starfish’s five arms corresponds to a copy of the conventional head-tail axis.

But efforts to definitively confirm these hypotheses were greatly hampered because methods for detecting gene expression, developed primarily in a small number of model organisms like mice and flies, don’t work well on juvenile starfish tissue.

By staining the genetic material with fluorescent labels, researchers can examine how key genes behave in the starfish's body
By staining the genetic material with fluorescent labels, researchers can examine how key genes behave in the starfish’s body | photo Laurent Formery

For years, Lowe and colleagues wanted to bring genetic insight to this question by mapping the activity of genes in developing starfish. But without the complex genetic tools developed over decades of research for typical model organisms, such an exhaustive analysis was daunting. Lowe found a solution in one of CZ Biohub’s SF meetings, where another researcher suggested contacting PacBio, a Silicon Valley company making genomic sequencing devices.

Their HiFi sequencing technique could now extract highly accurate data from intact gene-length DNA strands, making the process far quicker and cheaper than ever before. This was exactly what Lowe’s team needed to build a genetics study of starfish from scratch.

The findings unlocked new questions for further discovery about these unusual yet ecologically important creatures. Understanding starfish and their relatives not only helps solve key evolutionary mysteries but could also inspire medical innovations, as the researchers explained. More knowledge of their unusual anatomy and habitats may reveal unexpected strategies for staying healthy that could expand our methods for combating human diseases.

Sources

Chan Zuckerberg Biohub | University of Southampton | Formery, L., Peluso, P., Kohnle, I. et al. Molecular evidence of anteroposterior patterning in adult echinoderms. Nature (2023). doi.org/10.1038/s41586-023-06669-2

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