# Dissecting the cell-biological foundations of developmental cell signaling in a living animal

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2021 · $397,915

## Abstract

Project summary
How secreted signaling proteins act at a cell-biological level to orchestrate animal development and maintain
adult tissues is poorly understood. The research program described here seeks to elucidate how signaling
mechanisms at the molecular level are integrated with cell architectures and behaviors to regulate signaling in
space and time. Such knowledge will provide insights into essential mechanisms of development and
homeostasis. It will also have impacts relevant to human health as many of the same signaling pathways are
implicated in cancers and are key players in tissue engineering and regenerative medicine. The broad goal of
this program over the next five years is to dissect fundamental cell biological mechanisms that underlie cell-cell
signaling during development. Cells often use secreted signaling proteins to communicate at a range of
distances to regulate patterning and differentiation along with cellular behaviors such as migration and
morphogenesis. How these proteins move between cells to reach their destinations and activate signaling
remains largely unknown. We will use the worm C. elegans as a tractable model to investigate the cell
biological bases for these processes in a living animal. C. elegans is a powerful system to unravel mechanisms
due to the speed and efficiency of genome engineering, superb characteristics for live imaging, and a range of
methods for functional manipulations. The proposed work builds on prior efforts that identified essential
mechanisms that signaling proteins called Wnts use to disperse between cells and established experimental
systems to investigate other aspects of developmental signaling using advanced cell biology methods. Our
goals in the coming years are to elucidate: (1) functions for nerves in long distance Wnt signaling to non-neural
cells during development; (2) how spatial inputs from a cell signaling pathway are integrated with cell dynamics
to guide cell migration; and (3) how interactions between Wnts and other extracellular proteins control Wnt
spreading. Towards these goals, we will use a suite of approaches, including super-resolution live imaging,
genome engineering, and in vivo cell biology methods to interrogate developmental mechanisms with spatial
and temporal precision. Together, our efforts will provide novel and mechanistic insights into the cell biological
bases of animal development and build a framework for unique and sustained contributions.

## Key facts

- **NIH application ID:** 10275879
- **Project number:** 1R35GM142880-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Ariel Matthew Pani
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,915
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275879

## Citation

> US National Institutes of Health, RePORTER application 10275879, Dissecting the cell-biological foundations of developmental cell signaling in a living animal (1R35GM142880-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10275879. Licensed CC0.

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