# Local Role for Steroids in Regenerative Growth in Drosophila

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
The fruit fly, Drosophila melanogaster, is a well-established model system to define conserved mechanisms
that control proliferation, survival, invasiveness, and stem-like qualities of developing epithelia. A number of
clinically significant oncogenes and tumor suppressors have been discovered and defined in flies (e.g.
Yki/Yap1, Notch and archipelago/Fbw7), and multiple Drosophila tumor models are currently being used as
discovery platforms to identify potential therapeutic compounds and cocktails. The Drosophila Taiman (Tai)
and Yorkie (Yki) transcriptional co-activator proteins are the sole fly orthologs of the well-established human
oncoproteins SRC-3 and Yap1. Tai is the prime coactivator for the ecdysone receptor (EcR), a functional
homolog of nuclear hormone receptors, that controls many aspects of epithelial and stem cell development.
Yki is the main transcriptional effector of the Hippo pathway. Our laboratory discovered that Yki and Tai
physically associate on target gene promoters and that this Tai-Yki complex enables crosstalk between the
Hippo and steroid hormone pathways during developmental and pathologic growth in Drosophila.
 The current project is focused on a role for the Tai-Yki axis in homeostatic regrowth of wing epithelium
following wounding, and thus lies at the intersection of wound healing and cancer noted by Harold Dvorak’s
prescient description of cancer as “wounds that do not heal”. I have found preliminary evidence that transient
and local reduction in the ability of cells surrounding epithelial wounds to synthesize 20-hydroxyecdysone
(20HE), the steroid ligand of EcR, inhibits wound repair and regeneration. In parallel, I have found that EcR
transcriptional activity is also significantly induced within cells surrounding the wound. These data, in light of
the Tai-Yki complex, could link 20HE/EcR steroid signaling to Yki/Yap1-driven growth at the site of the wound.
Indeed, Tai supports expression of certain Yki pro-growth targets in uninjured discs that are upregulated during
regeneration (e.g. dIlp8). Thus, I will test the hypothesis that the steroid hormone 20HE is required for
imaginal wing disc regeneration through promoting transcriptional activity of Tai-dependent Yki targets. The
Specific Aims of this project are: 1) test the requirement for 20HE biosynthesis in wing disc regeneration; 2)
define the pattern of EcR activity in regenerating wing discs; 3) test the local requirement for the Tai-Yki axis in
regenerative growth. In Aim 1, I will compare the extent of regeneration of wing discs depleted of 20HE
biosynthesis genes to control discs, and determine the pattern of 20HE biosynthesis gene expression in
regenerating imaginal wing discs. In Aim 2, I will place EcR activation into the context with other pathways
activated during regeneration. In Aim 3, I will determine the effect of disrupting Tai-Yki association on the
extent of regeneration and Tai-dependent Yki target expression in wing disc...

## Key facts

- **NIH application ID:** 10071867
- **Project number:** 5F31CA239563-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Douglas Emmons Terry
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071867

## Citation

> US National Institutes of Health, RePORTER application 10071867, Local Role for Steroids in Regenerative Growth in Drosophila (5F31CA239563-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071867. Licensed CC0.

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