# Dependence for TEAD transcription factors in intestinal development and polyposis

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $362,016

## Abstract

SUMMARY
During vertebrate development, the visceral endoderm recruits adjacent mesoderm to form a primitive gut tube,
which later gives rise to the gastrointestinal (GI) tract. Organogenesis and tissue homeostasis within the GI tract
require continuous crosstalk between endodermal epithelium and the adjacent mesenchyme. Outstanding
studies in the field have elucidated the critical regulatory mechanisms controlling intestinal epithelial self-renewal
and regeneration. However, little is known about the biology of GI mesenchyme. During gut development, the
visceral mesoderm undertakes remarkable transformation during gut development; it differentiates from a thin
layer of progenitor cells into a complex tissue comprised of smooth muscle cells, fibroblasts, and endothelial
cells. More importantly, mesenchymal/stromal dysfunction is also closely associated with many digestive
diseases and cancers. Thus, understanding the genetic and molecular bases underlying mesenchymal growth
and differentiation may lead to future design of novel and effective therapeutic strategies for GI diseases. Our
recent work identified a previously unappreciated requirement of Hippo/YAP signaling in GI mesenchyme to
coordinate growth and patterning during embryonic development. The TEAD family transcription factors are
considered as the major mediator of Hippo/YAP signaling output; however, the physiological roles of TEAD
proteins in mammalian development remain poorly characterized. In this application, we will use a combination
of rigorous mouse genetics and chemical biology approaches to decipher the roles and underlying mechanism
of TEAD regulation in gut development and homeostasis. In Specific Aim 1, we will define the mechanism
underlying AP1-YAP/TEAD cooperation in gut mesenchyme. In Specific Aim 2, we will explore the YAP/TAZ-
independent TEAD function in gut development. In Specific Aim 3, we will use a chemical biology approach to
determine the functional significance of TEAD palmitoylation in hamartomatous polyposis. The successful
completion of the proposed studies in this application will provide significant progress towards our understanding
of the fundamental mechanisms underlying GI development, homeostasis and pathogenesis.

## Key facts

- **NIH application ID:** 10896334
- **Project number:** 5R01DK127180-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Junhao Mao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $362,016
- **Award type:** 5
- **Project period:** 2020-09-17 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896334

## Citation

> US National Institutes of Health, RePORTER application 10896334, Dependence for TEAD transcription factors in intestinal development and polyposis (5R01DK127180-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896334. Licensed CC0.

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