# Function of NF2/Merlin in regulation of the Hippo/Salvador/Warts growth control pathway

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $493,194

## Abstract

Neurofibromatosis type 2 (NF2), a dominantly inherited disease characterized by the
formation of bilateral vestibular Schwannomas (resulting in deafness) and other tumors,
is caused by loss of the tumor suppressor protein Merlin, a member of the FERM
domain superfamily. Studies using the fruit fly Drosophila and subsequently confirmed in
mammalian systems indicate that Merlin is an upstream component of the
Hippo/Salvador/Warts (HSW) pathway, a conserved signal transduction pathway that
regulates tissue growth. Mutations in Merlin and other HSW pathway components are
believed to cause tumors because they cause activation of an oncogenic protein
Yorkie/YAP and increased expression of growth promoting genes. Identifying specific
proteins and signal transduction pathways with which Merlin interacts is especially
important because these partners may act as genetic modifiers of NF2 disease
phenotypes and provide potential targets for therapeutic agents.
We seek to understand how Merlin and the other HSW components are organized into a
signaling complex at the cell cortex, what controls the activity of this complex, and how
feedback regulation operates within the pathway. We propose that Merlin and Kibra
nucleate formation of a signaling complex at a site separate from intercellular junctions,
and thus that these proteins can function in parallel to another upstream regulator,
Expanded. We also plan to study how cortical tension regulates pathway activity, and in
turn how pathway activity might control cortical tension. To address these questions, we
have developed tools and techniques that allow us to examine the localization and
dynamics of HSW pathway proteins expressed at endogenous levels in living tissues.
Using with the exquisite genetic tools available in Drosophila, we can now elucidate the
role of each pathway component in assembling and activating the HSW pathway. These
experiments are expected to provide insights into NF2, tumor suppression in general,
and the normal cellular processes that establish specialized membrane domains in
epithelial cells and neurons. Finally, these studies should contribute to work on the
mechanisms by which cellular interactions function to control tissue growth and
determine cell fate during development and regeneration.

## Key facts

- **NIH application ID:** 9977265
- **Project number:** 5R01NS034783-22
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Richard G Fehon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $493,194
- **Award type:** 5
- **Project period:** 1996-01-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977265

## Citation

> US National Institutes of Health, RePORTER application 9977265, Function of NF2/Merlin in regulation of the Hippo/Salvador/Warts growth control pathway (5R01NS034783-22). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977265. Licensed CC0.

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