# Upstream regulation of the Hippo signaling pathway

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $268,198

## Abstract

PROJECT SUMMARY
The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue
homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range
of human disorders, including cancer. Despite the well-established Hippo pathway core signaling cascade, the
upstream regulation of the Hippo pathway is less understood. Here we identified Drosophila Myotubularin
( Mtm) as a novel upstream regulator of the Hippo pathway. Loss-of-mtm caused tissue overgrowth with
elevated expression of diap1 and expanded, two most well-known Hippo pathway target genes. mtm mutant
flies also exhibited increased interommatidial cells and aberrant posterior follicle cell differentiation and
proliferation, hallmarks of Hippo signaling defects. Mtm is a member of the myotubularin family of
phosphoinositide lipid phosphatases with known function in controlling membrane phospholipid dynamics.
Consistently, we found that Mtm is membrane associated and binds to multiple membrane lipids. Our
preliminary studies also revealed a strong apical F-actin accumulation in mtm mutant cells. We therefore
hypothesize that Mtm is a novel upstream regulator of the Hippo pathway that regulates membrane
phospholipid dynamics and actin cytoskeleton remodeling. The goal of this project is to understand the
functional relevance of Mtm-mediated phospholipid dynamics and actin cytoskeleton remodeling in Hippo
pathway upstream regulation. The objective of this study is to elucidate the regulatory relationship between
Mtm and the Hippo pathway known components (Aim 1), to determine the role of Mtm on membrane
phospholipid dynamics and its functional relevance in Hippo pathway (Aim 2), and to define the downstream
cellular function of Mtm in Hippo pathway regulation (Aim 3). Accomplishment of this study will provide novel
mechanistic understanding of how Hippo pathway upstream signals are coordinated.

## Key facts

- **NIH application ID:** 10326704
- **Project number:** 7R01GM136904-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Jianzhong Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $268,198
- **Award type:** 7
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326704

## Citation

> US National Institutes of Health, RePORTER application 10326704, Upstream regulation of the Hippo signaling pathway (7R01GM136904-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10326704. Licensed CC0.

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