The basement membrane is a sheet-like extracellular matrix that wraps around muscle fibers and underlies epithelia. Because it has been difficult to study in vivo, the basement membrane is often considered to be static, analogous to cement. However, there are indications that the BM is a dynamic system. Basement membrane is able to grow, shrink, repair, and move to assist in tissue attachment as needed. We want to develop a system to analyze basement membrane repair in adult animals. In both mammals and flies, the gut appears to be a relatively dynamic basement membrane suggesting it could be a good system for analyzing repair.
We will analyze basement membrane repair using an adult gut injury model. The gut has a well-defined architecture of epithelial cells (enterocytes) residing on top of a basement membrane sheet, wrapped in visceral muscles also surrounded by basement membrane. To injure the gut, flies are fed Dextran Sodium Sulfate (DSS); DSS administration has been previously used as a model for ulcerative colitis in mice although the etiology is unknown. In Drosophila, DSS induces morphological changes in the architecture of the gut consistent with basement membrane damage. Using both electron and super-resolution microscopy, we observe an increase in BM thickness. Furthermore, preliminary data suggests that DSS becomes lodged in the gut BM. Interestingly, inhibiting or knocking down a collagen-IV crosslinking enzyme, peroxidasin, mimics the tissue changes seen in response to DSS. Currently, we are analyzing how this damage is repaired and the requirements for its repair. We plan to knock down multiple basement membrane components after flies reach adulthood to test their role in repair.