A human kidney relies on millions of specialized cells to filter waste, but not all animals have this luxury. For example, the tiny roundworm, Caenorhabditis elegans, relies on just one cell for this function. This lone cell, called the excretory cell, executes a stunning feat; starting as a solid structure, the excretory cell hollows itself and forms an H-shaped tube system that runs the entire length of the animal. Examining how cells such as the excretory cell hollow out to form tubes provides insights into related events in humans, such as how tiny capillaries in our circulatory system hollow out to form tiny tubes that connect arteries and veins.
In a new study published in the journal Development, researchers at the University of Wisconsin-Madison Center for Quantitative Cell Imaging have captured this microscopic remodeling project in unprecedented detail. By using worms that are genetically unable to twitch or wiggle, the research team led by Prof. Jeremy Nance was able to capture live videos of the cell building its own plumbing system.
“Although it was known that the excretory cell formed tubes, it had not been possible to study this process as it unfolded in living embryos because of the challenges imposed by embryos movements, which complicates imaging experiments.” Said Dr. Nance.
In biology, tubes can form through a variety of mechanisms that are familiar to anyone who’s shaped dough or worked with clay. Common ways for tubes to form are sheets wrapping around themselves or cylinders having their centers carved out, but making an H-shaped system within one cell requires something special. In this new study, Nance and his team found the C. elegans excretory cell tubes form when the cell’s outermost membrane grows inward to tunnel through the cell’s interior. They also found that the most critical challenge occurs when the tube tries to branch out to cover the worm’s whole body. To successfully spread, the cell must push through a stiff protective barrier known as the basement membrane.
To pass the basement membrane, the study shows that excretory cells rely on adhesion proteins called integrins.
Dr. Nance was focused on this class of proteins saying, “Integrins are cell surface proteins that bind to the basement membrane, allowing the cell to form adhesive connections with its outside environment.”
In this case, the integrins help the excretory cell anchor itself and push the newly formed tube through the tough barrier. The team found that when specific integrins were missing from excretory cells, the tubes can’t branch, fail to cross the basement membrane, and the excretory system remains incomplete.
“We found that in the absence of integrin, the excretory cell stopped extending when it reached the basement membrane, preventing the formation of its tubes.”
Humans don’t have single-cell kidneys, but our organs are packed with biological tubes. The mechanisms that worm cells use to produce tubes or push them through physiological boundaries are remarkably similar to the processes that human cells use. Working with roundworms is dramatically simpler than studying these same mechanisms in human organs and can help understand developmental defects where organs fail to form correctly or how cancer cells hijack these cellular mechanisms to spread and invade surrounding tissues.
“Our findings shed new light on how the smallest biological tubes form and also reveal the importance of integrins in invasion of cells across basement membranes in a living organism. Since tumor cells often have to invade basement membrane to migrate to new sites in the body, our findings also provide insights into how human cancers can spread.” adds Dr. Nance.
The Center for Quantitative Cell Imaging (CQCI) within the Office of the Vice Chancellor for Research at the University of Wisconsin-Madison is focused on advancing the fields of cellular and molecular biology. The CQCI emphasizes the development and application of cutting-edgeimaging technologies to visualize and measure biological processes at the molecular, cellular, and tissue levels. Faculty within CQCI have tenure homes or other appointments within the Departments of Cell and Regenerative Biology, Medical Physics, Biomedical Engineering, Biochemistry, Biomolecular Chemistry, Botany, and Integrative Biology. In addition, the CQCI manages the 3D Cell Electron Microscopy Core Facility. As a collaborative hub with the mission of sharing advanced imaging approaches across campus and with the broader scientific community, the CQCI aims to reveal the hidden mechanisms underlying cellular processes, health, and disease.