# Detecting cell to cell contacts in zebrafish with a synthetic receptor methodology

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2024 · $203,125

## Abstract

PROJECT SUMMARY
Signaling and adhesive interactions between neighboring cells play an important role in developmental
processes, helping determine cell fates and identities, migration pathways, and ultimately cellular function.
Currently the best method for characterizing cell to cell contacts is through ultrastructural studies. These
provide a wealth of information, but are technically complex, tedious to perform, and require extensive analysis
to identify specific interactions of interest.
We are working to develop a method of cell to cell contact tracing that provides useful information at the optical
microscopy level. Using synthetic notch receptors and the ligands they recognize, it is now possible to design
and genetically encode a touch sensitive detection system that operates in vivo. We have chosen the
CD19/synNotch receptor system utilized in CART therapy to detect contacts between cells. In our version,
recognition of the the CD19 ligand displayed on one cell surface activates a synNotch receptor on an opposing
surface, inducing the cleavage and release of a transcriptional activator that induces the expression of a
fluorescent marker protein.
We are working to perfect a cell to cell contact tracing methodology in the developing olfactory system of the
zebrafish. Zebrafish have a number of advantages for this study. Among them are excellent access to all
developmental stages, a rapid generation time, outstanding optical properties for imaging, and easy
transgenesis. The olfactory system has simple, well characterized circuitry and cell-specific promoters are
available to drive transgenic expression in specific classes of olfactory sensory neurons. The aim of this project
is to identify the cells an olfactory sensory axon contacts as it extends from its origin in the olfactory epithelium
to its target in the olfactory bulb. This information is crucial for understanding how these sensory axons home
in on specific target regions within the bulb.

## Key facts

- **NIH application ID:** 10795675
- **Project number:** 5R21DC021001-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JONATHAN A RAPER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $203,125
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795675

## Citation

> US National Institutes of Health, RePORTER application 10795675, Detecting cell to cell contacts in zebrafish with a synthetic receptor methodology (5R21DC021001-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10795675. Licensed CC0.

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