# Systematic Reconstruction of Epithelial-Mesenchymal Communication in Organ Development

> **NIH NIH DP2** · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 2021 · $1,755,000

## Abstract

PROJECT SUMMARY
Mesenchymal cells are major components of tissue stroma and best known for their role in supporting the
physical structure of organs. They juxtapose to and communicate with epithelial cells, to control organ
development in embryos, and to regulate tissue inflammation, injury repair and cancer progression in adults.
Traditionally, mesenchymal cells in different organs were thought to perform similar functions. However, recent
studies have revealed unexpected diversity of gene expression signatures among mesenchymal cells from
different organs. Such diversity is likely to play a crucial role in regulating mesenchymal-epithelial interactions
and thus organ development and physiology. The overarching goal of this proposal is to understand how
epithelial-mesenchymal interactions control organogenesis across different organs. To achieve this goal, we will
first address the question of how mesenchymal diversity arises as the consequence of distinct signaling histories.
We will develop a novel high-throughput system to simultaneously test tens of thousands of signal combinations.
We will then investigate how epithelial-mesenchymal interactions control tissue morphogenesis, by reconstituting
and genetically perturbing such interactions ex vivo. We are especially interested in comparing the specificity
and plasticity of epithelial-mesenchymal interactions across different organs, and identifying the role of
extracellular matrices that are shared by epithelial and mesenchymal cells in controlling morphogenesis. We will
closely integrate experimental measurements with computational models to produce a quantitative framework
for understanding organ morphogenesis. By integrating tools and materials from diverse fields, we will gain a
fundamental understanding about the developmental origin and functional implications of the long-overlooked
mesenchymal cells. These insights and tools will enable the engineering of organoids to better model
development and diseases, and will advance the field of tissue engineering.

## Key facts

- **NIH application ID:** 10246013
- **Project number:** 1DP2HD108777-01
- **Recipient organization:** WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
- **Principal Investigator:** PULIN LI
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,755,000
- **Award type:** 1
- **Project period:** 2021-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246013

## Citation

> US National Institutes of Health, RePORTER application 10246013, Systematic Reconstruction of Epithelial-Mesenchymal Communication in Organ Development (1DP2HD108777-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10246013. Licensed CC0.

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