Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

How shapeless blobs of cells grow into wriggling worms

AUSTIN, TEXAS—A newborn infant looks unmistakably human, with legs, mouth, ears, and bottom all in place. The same can’t be said about the youngest sea stars, worms, or butterflies: Many invertebrates start out looking nothing like the adults they will become. Now, researchers have monitored one worm’s larval cells during the transformation to adulthood, spying on their fates and how their identities changed. The work, reported earlier this month at the annual meeting of the Society for Integrative and Comparative Biology here, provides some of the first clear cell-by-cell clues about what happens during these radical changes in body form.

“We are beginning to get at how a larva produces an adult body plan,” says Christina Zakas, an evolutionary biologist at North Carolina State University (NCSU) who was not involved with the work. The study’s reliance on a sophisticated technique for tracking gene activity in single cells is also a milestone. To date, most single-cell analyses have focused on well-studied “model” animals such as the fruit fly, mouse, or zebrafish. “That [the author] got this new technology to work on something that was not a model organism was just stunning,” says Greg Rouse, a marine biologist at the Scripps Institution of Oceanography who was not involved with the work. The work could inspire other biologists to study their own favorite metamorphosis at the level of single cells, he says.

Invertebrates undergo several kinds of larva-to-adult transformations. Caterpillars become butterflies through a well-understood process called catastrophic metamorphosis, in which a small group of cells that were dormant in the larva multiply and diversify into the adult, leaving the dead larval body behind. But Paul Bump, now a postdoctoral fellow at Harvard University, wanted to know what happens in species lacking such a group of cells.

Bump, who was then a Stanford University graduate student working with evolutionary biologist Christopher Lowe, focused on the California broken-hearted worm (Schizocardium californicum), a marine worm found in California mud flats. The 30-centimeter-long adult grows out of a larva that is little more than a sesame seed–size blob with an eyespot at one end and a band of cilia around its body. Several months after starting life, in just 48 hours or so, the larva transforms into a tiny juvenile worm with bulging mouthparts, a thickened midsection, and a long, sinuous body.

The adult California broken-hearted worm can measure 30 centimeters and looks nothing like the sesame seed–size larva.P. GONZALEZ ET AL., CURRENT BIOLOGY (2016) 10.10.16/J.CUB.2016.10.047

To track what happens to the larva’s cells as it transitions to adulthood, Bump and his colleagues first sequenced the worm’s genome and figured out how to tease out individual cells. He measured gene activity in cells isolated from larvae at different stages of metamorphosis and from the juvenile worm. Using those results, he grouped the larval and juvenile cells into different types—nerve cells, muscle cells, and the like. He also attached labels to DNA at different time points so he could see where it—and the cell containing it—wound up as metamorphosis proceeded.

The method could even identify cells that formed during metamorphosis. The protocol is “a new way of asking questions about cell identities,” says Caroline Albertin, a developmental biologist at the Marine Biological Laboratory who was not involved with the work.

Depending on the cell type, one of three things happened. Muscle cells and some other cell types survived the transformation with little change. Other larval cells, including a few nerve cells, died off and disappeared. But to Bump’s surprise, many cells—perhaps almost half, including other nerve cells and gut cells—seemed to hang around but switched their repertoire of active genes, taking on different roles in the adult. “What a cell is, and is capable of, is more flexible than we previously appreciated,” he said at the meeting. “It seems that there are different cell types at different developmental stages,” says Jose Aguilar, an evolutionary biologist at NCSU who hopes to use the single-cell technique in his own work on other worms.

Bump also noted clues to the evolutionary roots of metamorphosis. Around the time the worm’s larva began its transformation, many cells started to produce an enzyme that, in insects, helps activate a molecule called juvenile hormone. The worm appears to make a related hormone, Bump reported, and the timing suggests the hormone plays a role in the worm’s metamorphosis. Because the juvenile hormone is known to regulate metamorphosis in insects, the finding could mean that some of the molecular mechanisms controlling the process evolved in a common ancestor of worms and insects.

Elaine Seaver, a developmental biologist at the University of Florida, suggests more insights may be forthcoming. “We’re starting to apply single-cell sequencing to all kinds of animals. It’s a powerful tool to learn more about evolution and about life histories.”

Source link

Leave a Reply

Your email address will not be published.