# Regulation of organogenesis through regional variations in tissue mechanics

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $471,438

## Abstract

ABSTRACT
The long-term goal of the proposed research is to understand the mechanisms that regulate organogenesis.
The overall objective of the proposal is to use our novel in vivo force transducers, which allow quantitative
measurements of mechanical stresses within living embryonic tissues, to unveil the role of mechanical signals
in the specification of signaling centers and cell types during organ morphogenesis, using the tooth as a model
system. The central hypothesis is that the endogenous regional variations in compressive and tensile
stresses in the tissue control the distribution of nuclear YAP localization in the developing tooth, thereby
regulating specification of key signaling centers. The following Specific Aims will employ a combination of
novel technologies designed to measure mechanical stresses in vivo and in situ with sophisticated mouse
genetic strategies. Aim 1 will characterize regional differences in endogenous compressive and tensile
stresses during tooth development. These experiments will constitute the first ever measurement of regional
differences in compressive and tensile stresses during the formation of any vertebrate organ. These regional
changes in mechanics will be related to spatial variations in YAP nuclear localization in the tissue and the
establishment of signaling centers. Aim 2 will determine the molecular control of signaling center
formation by tensile and compressive stresses in the developing tooth in vivo. In order to link the in vivo
stress measurements to the molecules controlling the mechanical phenotype, we will first image the
spatiotemporal distribution of proteins involved in force generation. Moreover, we will genetically delete the
genes encoding these proteins and determine how mutations in these genes affect YAP localization and the
ability to generate compressive and tensile stresses in the tissue. Aim 3 will reveal the role of mechanical
stresses in the regulation of nuclear vs. cytoplasmic YAP localization in vivo. These experiments will
directly test our hypothesis that regional differences in compressive and tensile stresses in the tissue control
the tissue distribution of nuclear YAP localization. Together, these studies will provide a leap forward in our
knowledge of how tooth development is regulated by a novel signal, mechanical stress. Such information about
the fundamental biology of tooth development will in turn enhance future efforts in applications such as tooth
bioengineering.

## Key facts

- **NIH application ID:** 9853010
- **Project number:** 5R01DE027620-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Otger Campas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $471,438
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853010

## Citation

> US National Institutes of Health, RePORTER application 9853010, Regulation of organogenesis through regional variations in tissue mechanics (5R01DE027620-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853010. Licensed CC0.

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