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Title page for ETD etd-03222019-152412

Type of Document Dissertation
Author Howard, Angela Marie
Author's Email Address angela.howard@vanderbilt.edu
URN etd-03222019-152412
Title Basement Membrane Homeostasis and Repair
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Alissa Weaver Committee Chair
Andrea Page McCaw Committee Member
Chin Chiang Committee Member
Gautam Bhave Committee Member
Matthew Tyska Committee Member
  • Basement Membrane
  • Dextran Sodium Sulfate
  • Drosophila
Date of Defense 2019-03-01
Availability unrestricted
The basement membrane is a sheet-like extracellular matrix that wraps around muscle fibers and underlies epithelia. Although the basement membrane is often considered to be static, there are indications that the BM is a dynamic structure in vivo, as it can grow, shrink, and repair. We have developed a system to analyze basement membrane repair in adult animals, using an adult gut injury model in Drosophila. The gut has a well-defined architecture of epithelial cells (enterocytes) residing on top of a basement membrane sheet, and the gut tube is wrapped in visceral muscles also surrounded by basement membrane. Here we show that Dextran Sodium Sulfate (DSS) directly damages the gut basement membrane when fed to adult Drosophila. DSS becomes incorporated into the basement membrane, promoting its expansion while decreasing its stiffness, which causes morphological changes to the underlying muscles. Remarkably, two days after withdrawal of DSS, the basement membrane is repaired by all measures. We used this new damage model to determine that repair requires collagen crosslinking and replacement of damaged components. Genetic and biochemical evidence indicates that crosslinking is required to stabilize the newly incorporated repaired collagen IV rather than to stabilize the damaged collagen IV. These results suggest that basement membranes are surprisingly dynamic.
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