# Basement membrane repair dynamics in the Drosophila midgut

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $25,670

## Abstract

Basement membranes are the oldest, most conserved forms of extracellular matrix and serve to separate tissue
layers, direct signals to neighboring cells, insulate tissues from signals, and provide mechanical support. Further,
basement membranes are subject to mechanical damage and require repair. Faulty basement membrane repair
can aid in the progression of diseases such as asthma and diabetes, and diseases of the basement membrane
itself, including Alport syndrome and Goodpasture syndrome. Therefore, understanding how basement
membranes repair will be vital to treating these conditions. My work utilizes the Drosophila midgut basement
membrane to probe repair dynamics. In Drosophila, all major basement membrane components have been
conserved but with less redundancy than mammals. Our lab has developed an assay to reproducibly damage
the basement membrane and study the repair process. Following damage, the basement membrane becomes
less stiff and less dense, indicated by a mechanical stress/strain assay and electron microscopy, respectively.
Previously it was reported that processes required for basement membrane repair are also required to maintain
basement membranes that have not been damaged; these processes include continuous matrix synthesis and
regulation of enzymes (matrix metalloproteinases and peroxidasin). Thus, it is unclear whether basement
membrane damage is actively detected, or instead, passively repaired by homeostatic mechanisms. My
preliminary data suggest basement membrane damage is actively detected. Following damage, the synthesis of
matrix components is upregulated in a specific subset of gut epithelial cells we call matrix-makers, and these
may be the same cells that express a mechanosensory stretch-activated ion channel, Piezo. This raises the
possibility that a change in stiffness of damaged basement membranes signals the initiation of repair. Piezo
knockout flies are able to assemble and maintain basement membranes in the adult fly, but, excitingly, Piezo
knockouts cannot repair basement membranes after damage. This is evidence of a unique mechanism that
detects basement membrane damage and initiates repair. I hypothesize that a loss in matrix stiffness triggers
basement membrane repair mechanisms. In Aim 1, I propose to characterize a transient cell population
responsible for synthesizing new matrix components following basement membrane damage. In Aim 2, I
propose to identify the role of Piezo and its response following basement membrane damage. I expect to identify
the first mechanism for detecting and repairing basement membranes. Understanding this mechanism will
provide fundamental insights into epithelial biology and will be critical to treating and understanding diseases of
the basement membrane.

## Key facts

- **NIH application ID:** 10913445
- **Project number:** 5F31GM148021-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** AUBRIE STRICKER
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $25,670
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-05-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913445

## Citation

> US National Institutes of Health, RePORTER application 10913445, Basement membrane repair dynamics in the Drosophila midgut (5F31GM148021-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10913445. Licensed CC0.

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