The basement membrane toolkit: Looking outside the cell
Basement membranes are an ancient form of extracellular matrix that assemble as thin, dense sheets that underlie most tissues. Basement membranes regulate numerous cellular and tissue functions, and basement membrane dysregulation is a hallmark of many cancers and a driver of tumor progression. Despite their importance, we know little about how basement membranes are uniquely constructed, how they grow, how they turnover, and how they regulate so many cell and tissue properties.
C. elegans is a powerful model to understand basement membrane function, as it has single genes encoding most basement membrane matrix components and receptors. We have used CRISPR/Cas-9 genome editing to create a basement membrane toolkit, where we have knocked genes encoding fluorescent proteins into all major basement membrane matrix components (18 genes) and receptors (13 genes). I will present a brief overview of how we are using the basement membrane toolkit to elucidate how basement membranes are constructed, how they grow, and the dynamic nature of basement membranes, including diverse turnover rates of basement membrane components (seconds to hours). Finally, I will discuss how the toolkit is revealing specialized, non-sheet functions for basement membrane proteins, such as linking neighboring tissues together and constructing stem cell niches.
David Sherwood, Ph.D., grew up in Champaign, Illinois, and spent summers backpacking in the Wind River Range of Wyoming. He graduated from Illinois Wesleyan University (with a year in Durham, England) in 1990. He received his Ph.D. in the lab of David McClay, Ph.D., from Duke University Department of Biology in 1997, where his thesis work identified and determined the function of the sea urchin Notch receptor. Dave carried out his postdoctoral work in the lab of Paul Sternberg, Ph.D. at the California Institute of Technology, where he was trained in C. elegans genetics and cell biology. He joined the faculty at Duke University in 2005, where he is now a Professor of Biology, Co-Director of the Regeneration Next Initiative for Regenerative Biology, Director of the Development and Stem Cell Biology Program, and Co-Director of the Embryology Course in at the Marine Biological Laboratory in Woods Hole, Massachusetts. His research focuses on elucidating cell-extracellular matrix interactions that occur during cell invasion, stem cell niche formation, and tissue formation, growth and regeneration.