# Principles of Mechanochemical Signal Integration Underlying Developmental Robustness

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $372,100

## Abstract

Project Summary / Abstract
My research program aims to understand cellular mechanisms underlying robust embryonic tissue
patterning. Despite environmental fluctuations, tissues develop nearly identical patterns, shapes, and
sizes among different stage-matched individuals. In contrast, artificial tissues grown in vitro are highly
variable, limiting their value for disease modeling. How single cells can reliably sense and control
tissue parameters remains an important open question in both developmental biology and tissue
engineering.
Departing from the traditional focus of patterning control by biochemical signaling, my research aims
to understand how cells integrate biochemical and mechanical signals to detect and respond to
changes in tissue pattern and shape. We are empowered by our expertise in in vivo live imaging,
zebrafish genetics, computational modeling, and innovative approaches to manipulating tissues’
biochemical and mechanical environments. Using these multidisciplinary tools, we will test how cells
incorporate mechanical information to detect tissue-scale changes that are challenging to detect by
morphogen signaling alone. First, we will determine whether cells can sense the cell type identity of
their neighbors through cadherin-based adhesion, and use this information to modify cell fate
decisions and correct errors in tissue patterning. Second, we will identify mechano-responsive
morphogen signaling pathways and investigate whether mechanochemical crosstalk allows the cells
to infer their relative positions more accurately in tissues undergoing morphogenesis.
By revealing how tissue parameters are encoded by biochemical and mechanical signals, and how
cells decode mechanochemical signals to sense and control changes in tissue parameters, our
research will elucidate the information flow from tissue-scale changes to cellular responses. Our work
will establish cell adhesion and mechanical force as key channels of tissue information directing
accurate cellular decisions in early tissue patterning events, a novel paradigm that will impact our
understanding of development, mechanical consequences in diseases, and engineering strategies for
artificial tissues.

## Key facts

- **NIH application ID:** 10932878
- **Project number:** 5R35GM150759-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Tony Yu-Chen Tsai
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $372,100
- **Award type:** 5
- **Project period:** 2023-09-22 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932878

## Citation

> US National Institutes of Health, RePORTER application 10932878, Principles of Mechanochemical Signal Integration Underlying Developmental Robustness (5R35GM150759-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10932878. Licensed CC0.

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