Developing Frankenfrogs hold clues to the secrets of body plan formation

Almost nothing is more daunting than assembling your first IKEA piece. Most fully realized adults attack the picturebook manual with gusto, only to stumble in their path to independence; clearly these furnishings require back-up. Soon, it becomes apparent that team work may not make the dream work, as each partner interprets the deceptively complex coloring book differently. As hours turn to days, authoring yet another argument, every MALM or EKENÄSET seems destined to break apart even solid relationships.

But if IKEA thinks it has cornered the market on building complex structures, it could take a page from the developmental biology manual. Like a couple just trying to assemble their hopes and dreams, cells have to work together to build a body. Every cell in the body has instructions encoded in its DNA to construct a functioning body after fertilization. Biologists have come a long way in understanding how this happens, from using macabre dissection at the turn of the 20th century, to more modern genome editing in the 21st. But there are still many questions, like if and how do bodies resolve conflicting instructions when building such grand designs.

Vasilios Nanos, a doctoral student working with Michael Levin at Tufts University, has set out to answer this question by mixing old techniques with new technologies. The familiar frog – a staple in biology classrooms – is his first contractor to understand how bodies are built. The second is the axolotl, a salamander from Mexico famous for its dopey face and regenerative abilities.

Amphibians have been used in developmental biology since the 19th century because they have large embryos that develop outside a shell or womb, allowing for easy visualization of moving and growing parts. This long history has allowed a myriad of techniques to proliferate, from cellular dissection to genetic engineering. Cells from the axolotl salamander have instructions to build a salamander tail, and the frog its own. When mixed on a single animal, you can see if and how the cells cooperate to build a successful swimmer. Victor Frankenstein could do no better as Nanos surgically grafts the developing tail of a salamander onto that of a tadpole to see what happens. “It’s like playing legos”, he says of the modularity of these ‘frogolotls’ – a portmanteau of ‘frog’ and ‘axolotl’ – easily swapping body parts from one creature to the next.

Although these chimeras are only in their preliminary stages, Nanos has found that the cellular construction crews are finding ways to communicate. Systems from the two different organisms are working together, as nerves, veins, and immune cells between the frog body and salamander tail intertwine. Sounding more fiction than science, Nanos hopes to decode the algorithms used to construct body plans, with implications for developmental disease, cancer, or other realms of synthetic biology. Maybe then he can even help us build a befuddling SKRUVBY or monstrous MÖRBYLÅNGA.

Nanos will present these results at the Society for Integrative and Comparative Biology’s Annual Meeting in Seattle, Washington in January 2024.

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