Basement Membranes Mediate Interactions Between Tissues

Abstract

<p>Basement membranes (BMs) are conserved, cell-associated, sheet-like networks of extracellular matrices that provide structural support to tissues. BMs also function as a signaling scaffold, directing cellular processes including self-renewal, adhesion, and proliferation. However, the role of BMs in mediating interactions between tissues is an active area of inquiry. Using C. elegans, which are highly amenable to genetic and visual manipulation, I investigated the role of BMs in mediating inter-tissue interactions within the reproductive system: in tissue separation (gonad and body wall muscle), in tissue linkage (uterine utse and epidermal seam), and in stem cell-niche interactions (germ stem cells and niche). To probe BM function, I used live-cell imaging of endogenous localization of BM components, conditional knockdown, RNAi screening, and genetic mutant alleles. In Chapter 1, I discuss what is known about BMs in the separation and linkages of reproductive tissues, BM function in the germ stem cell niche, and introduce the advantages of using C. elegans as a model. In Chapter 2, I explore the role of BMs in mediating niche enwrapment. In Chapter 3, I show that failed BM separation between the gonad and body wall muscle leaks germ cells into the body cavity to become enwrapped by abnormally protrusive muscle cells. In Chapter 4, I find that discoidin domain receptor-2 directs adhesion of uterine utse BM and epidermal seam BM to connect reproductive tissues. In Chapter 5, I discuss the impact of these findings.</p>