Consider the papercut—a minor injury best known for the disproportionate amount of pain it can cause. That a wound so inconsequential can sting so terribly is curious, but perhaps even more surprising is the fact that it heals at all.
To heal a wound, even one as trivial as a papercut, the cells involved in the repair must migrate to precisely where they’re needed at the site of injury. Determining where to go requires interpretation of a substantial number of factors, including chemical signals, fluid dynamics, mechanical properties, and more. Cells also migrate in other, similarly complex circumstances, from embryonic development to cancer metastasis.
Most of what we know about how these feats are controlled has come from in vitro studies with cells growing in essentially two-dimensional layers in Petri dishes. Although this research continues to provide invaluable insights, in vitro studies alone can’t give a complete understanding because cells grown in such conditions don’t move exactly the way cells in the body do. In GENETICS, researchers David Sherwood and Julie Plastino review how studies using the microscopic nematode Caenorhabditis elegans are improving our understanding of cell migration.
Sherwood and Plastino explain several reasons that C. elegans is an especially good model for this kind of research. The worms’ simplicity makes them easier to study, and many aspects of cell migration are conserved from C. elegans to humans. C. elegans’ status as one of the best-established model organisms means researchers can take advantage of established protocols to genetically manipulate and study the worms. The worms are transparent, making tracking cell migration less complicated. Also helpful is the fact that the worms develop in a very predictable, choreographed way: hermaphrodites (which, in worms, are essentially females) have precisely 959 body cells, while males have 1031 body cells.
Cell migration in the worms takes many forms, some of which the authors discuss in the review. In one example, they describe how cells penetrate basement membranes, which are thin but tough layers of extracellular matrix found in animals. In humans, basement membranes attach surface cells—such as the top layers of skin and the lining of blood vessels—to the underlying connective tissue. Basement membranes act in part as cellular gatekeepers, preventing cells from escaping tissues. Human basement membranes, however, must be punctured in a variety of circumstances, such as when new blood vessels need to grow through the membranes and when cancer cells spread.
Most C. elegans tissues are encased in basement membranes, and as in humans, these membranes must sometimes be breached. During the worms’ development, a type of uterine cell called an anchor cell burrows through a basement membrane that separates the vulva from the uterus. This infiltration links the organs together, allowing the worms to mate and lay eggs.
Studying how anchor cells invade the basement membrane in C. elegans has produced numerous insights into human cell migration—both normal and pathological. In 1989, scientists first reported in vitro observations of invasive tendrils they called invadopodia protruding from cells grown on a simplified extracellular matrix, including cells from established cancer cell lines and primary tumor cells.
Later, C. elegans researchers found invadopodia on anchor cells penetrating the basement membrane, providing the first evidence that the structures exist not only in cells grown in vitro, but also in a whole animal. They also discovered some discrepancies between the characteristics of invadopodia in cells grown in vitro and C. elegans cells, which could reflect differences in how invadopodia behave when subjected to the full range of stimuli present in vivo.
In the review, Sherwood and Plastino highlight many more discoveries about cell migration that have been made—and continue to be made—using C. elegans. All evidence indicates that C. elegans will remain a valuable asset to the field, serving not only as a link between in vitro studies and investigations of more complex animals such as humans, but also as a rich source of fundamental discoveries in itself.