# Tissue flow genetics: using cartography to reveal forces driving morphogenesis

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2020 · $248,999

## Abstract

ABSTRACT 
The form that organs acquire during development is critical for their functionality. For example, failed tissue 
looping during heart development results in congenital heart disease -­ the most common birth defect observed 
in humans. While many studies have identified how cells are fated to perform their tasks, we know little about
the forces that shape tissues. Transcription factors (TFs) spanning multiple length scales - ranging from a few
to hundreds of cells - precisely regulate gene expression programs. These programs generate the physical
stresses that give rise to cell behavior. To ensure that organs take on their proper shape vital for their function,
physical stresses must be coordinated across tissues spanning multiple length scales. We are beginning to
understand how short-ranged TFs control physical stresses at the level of individual cells. This proposal seeks
to uncover how tissues are shaped by physical stresses, controlled at the organ scale, using D. melanogaster
as a model system.
Novel methods for in toto live imaging and tissue cartography have revealed: cell behavior is modulated along
the dorsoventral (DV) axis during germband extension. DV behavior modulation is lost in dorsalizing mutants.
These findings challenge the assumption, that long-range TFs, such as Dorsal, act only indirectly by setting up
short-range patterns to control stress. To test the hypothesis that long-range TFs modulate physical stresses
responsible for organ shape, we propose: Aim 1 to measure physical stress at the organ scale, and by
systematic comparison to known TF expression patterns, identify the role of Dorsal in organ scale stress
coordination. In aim 2 we will extend our observations to investigate coordination of cell behavior across
heterologous tissue layers during midgut looping.
The proposed research combines quantitative experiments with theory, to provide the first strategy for
measuring TF mediated global stress coordination that shapes organs. State of the art microscopes and tools
designed for analyzing cell behaviors that produce complex shapes will open new opportunities for
understanding how intricate organs form, including loops.

## Key facts

- **NIH application ID:** 9813556
- **Project number:** 5R00HD088708-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Sebastian J Streichan
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2017-11-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9813556

## Citation

> US National Institutes of Health, RePORTER application 9813556, Tissue flow genetics: using cartography to reveal forces driving morphogenesis (5R00HD088708-05). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/9813556. Licensed CC0.

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