# Dissecting Fat cadherin function in vivo

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $455,399

## Abstract

Fat cadherins have critical and conserved roles in coordinating tissue growth and tissue organization. How
these cell-adhesion molecules coordinately control growth and patterning is still not well understood. To
address this need, we have initiated comprehensive CRISPR-based mutagenesis of Drosophila ft in vivo, and
used endogenous Ft tagged with GFP to identify co-immunoprecipitating proteins with mass spectrometry.
Fine-scale mutagenesis of endogenous ft indicated Ft has critical roles in control of bilateral symmetry.
Proteomic studies of endogenous complexes revealed nuclear proteins that interact with Ft, suggesting novel
functions of Ft in transcriptional regulation. To investigate these roles of Ft we propose three specific Aims.
1. Delineate growth and PCP domains and define protein interactors in vivo. We will use in vivo gene
editing approaches to define domains of Ft that regulate planar cell polarity (PCP) tissue organization and
growth. Using endogenous Ft-GFP, we identified novel in vivo Ft binding partners. We will confirm these
interactors and investigate their functional relevance.
2. Define the function of Ft in fluctuating asymmetry (FA). Deletion of a region of Fat that is highly
conserved in Drosophila and humans results in viable flies that have lost fine control of bilateral symmetry.
This implies Ft has a role in mechanisms underlying bilateral symmetry, and functions to sense or implement
fine-scale organ checkpoints. We will test if alterations in known outputs of Ft (PCP, Hippo or mitochondrial
function) are responsible for FA, and test if genes implicated in FA are affected by Ft. We will determine the
tissue specificity of Ft in restricting FA, and investigate proteins that bind the D region for function in FA.
3. Define the function of Ft in the nucleus. We found the cytoplasmic domain of Ft can localize to the
nucleus and interact with chromatin remodeling complexes. We will define NLS and NES sequences, and
determine the consequences of deleting those sequences in the endogenous locus. We will determine if
nuclear Ft specifically affects Hippo, PCP signaling or metabolism, and investigate Ft transcriptional regulation
of target genes. RNAseq, ChIP-seq and in vivo reporter analyses will be used to determine the function of
nuclear Ft.
If successful, these studies will illuminate novel functions of Ft in control of bilateral symmetry and
transcription, and provide mechanistic insight into regulation and integration of Ft’s diverse functions in vivo

## Key facts

- **NIH application ID:** 10225527
- **Project number:** 5R01GM138853-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Helen McNeill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $455,399
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225527

## Citation

> US National Institutes of Health, RePORTER application 10225527, Dissecting Fat cadherin function in vivo (5R01GM138853-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225527. Licensed CC0.

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