Animals that sexually reproduce are fundamentally made up of two types of cells: germ cells that produce gametes (sperm and eggs), and somatic cells that complete the body.
Once germ cells are formed, they are set aside for reproduction. While somatic cells die off with each generation, germ cells live on through the “immortal” genetic material that gets passed on from generation to generation.
She studies planarians, flatworms that have an amazing ability to regenerate both somatic cells and germ cells from pluripotent stem cells called neoblasts—which make them an ideal model organism to answer her questions.
In a recent study published in the journal PLOS Biology, Issigonis describes genetic factors that support the development of germ cells, and surprisingly were also found in specialized yolk cells, part of a unique reproductive organ in the planarian flatworm.
Issigonis and her team looked for factors important for specifying new germ cells by using a technique called fluorescent RNA in situ hybridization (FISH) to examine gene expression. They discovered a new gene that is homologous to a well-known mammalian pluripotency factor, Krüppel-like factor 4 (klf4).
They named the homolog klf4-like.
The researchers found that klf4-like was expressed in primordial germ cells of newborn planarian hatchlings, as well as in the germline stem cells of the ovaries and testes of sexually mature adult flatworms.
In addition to their extraordinary regenerative ability, planarians also reproduce in a notable way—they are hermaphrodites, containing both male and female gonads in a single organism. They are also ectolecithal, meaning they have yolkless eggs. Instead, the nutrient-rich yolk is on the outside of the egg, produced by specialized yolk cells.
Issigonis and colleagues observed that klf4-like was also expressed in these yolk cells.
“Yolk cells are generated by a whole different organ system called the vitellaria,” she explains. “It is a unique evolutionary innovation that only happens in flatworms.”
The vitellaria are also structurally analogous to the gonads. Testes and ovaries are made up of somatic cells that send signals to support and develop germ cells. And vitellaria have niche somatic cells that support yolk cell production.
After noting that both germ cells and yolk cells expressed klf4-like, the researchers tested gene function via RNA interference, a technique that knocks down or reduces gene expression.
They found that germ cells lost their ability to make sperm and eggs; similarly, yolk cell production in the vitellaria was suppressed—as a result, the planarians became sterile and could no longer reproduce.
Anything that we can study and learn about their reproduction can give us clues for how we can combat these parasites. You really want to target something that’s unique to them.Melanie Issigonis
In addition to klf4-like, the yolk cells also expressed other genes that are well-known and conserved in germ cells, such as nanos and piwi.
“There are some intriguing similarities there, which as developmental biologists we’re really interested in studying,” she says.
Evolutionarily, this is important because not all flatworms are ectolecithal. Some do have yolky eggs—they are endolecithal—and they don’t have the vitellaria organ system. So at some point, there was a change from having one reproductive organ system to two.
“It’s possible that yolk cells evolved from germ cells, and we’ve provided molecular evidence for this,” Issigonis says. “Yolk cells look and behave like germ cells; they’re similar in many ways.”
While planarians are free-living flatworms (found in freshwater), they are closely related to parasitic flatworms, like schistosomes and tapeworms. They are all characterized by having vitellaria.
“This evolutionary quirk or innovation evolved and is now shared between parasitic and non-parasitic flatworms,” Issigonis says. “Anything that we can study and learn about their reproduction can give us clues for how we can combat these parasites. You really want to target something that’s unique to them.”
Moving forward, Issigonis hopes to make more discoveries on the developmental similarities between gonads and vitellaria, but also wants to characterize their differences to circle back on her big picture question: how are germ cells made?