# Molecular control of tissue morphogenesis

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $337,197

## Abstract

A fundamental property of cells is their ability to act collectively to generate functional
multicellular structures during tissue development, regeneration, and repair. An understanding
of the mechanisms that organize cells into tissues is essential for treating developmental
disorders and realizing the potential of tissue engineering and regenerative medicine. Cell-
surface receptors expressed in precise patterns across tissues create spatial maps that control
local interactions between cells and organize collective cell movements to establish tissue
structure. How dynamic cell behaviors are organized in response to complex patterns of
extracellular spatial information is not well understood. During convergent extension, the
movements of hundreds of cells are systematically aligned with the tissue axes to elongate the
body axis. This proposal aims to understand the mechanisms that regulate dynamic changes in
cell polarity and interactions during this process, and to elucidate how cells respond to complex
patterns of spatial information to achieve this conserved tissue structure. We discovered that
three cell-surface proteins in the Toll receptor family create a spatial map that guides cell
movements during convergent extension in Drosophila and directs the localization and activity
of cellular proteins that generate contractile and adhesive forces within cells. Vertebrate Toll-like
receptors respond to an extraordinary range of signals presented by fungi, bacteria, viruses,
and parasites to elicit transcriptional changes that activate the innate immune response, but the
mechanisms required for Toll receptor activation and signaling during convergent extension are
not well understood. We will use genetic, cell biological, biochemical, and quantitative imaging
approaches to determine how Toll receptors promote selective recognition between cells during
development and identify the signaling mechanisms by which these receptors regulate cell
polarity and behavior. Powerful genetic, cell biological, and quantitative imaging methods in
Drosophila will be used to dissect the distinct spatial inputs of different members of this family of
cell-surface receptors and investigate their functional contributions to cell behavior and tissue
morphogenesis. These studies will elucidate mechanisms of Toll receptor activation and
signaling and reveal general principles of tissue organization. A better understanding of how
extracellular spatial cues are translated into changes in cell polarity and dynamics to establish
tissue structure can provide insight into how the deregulation of these processes contributes to
developmental disorders and human disease.

## Key facts

- **NIH application ID:** 9983685
- **Project number:** 5R01GM079340-12
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jennifer A Zallen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,197
- **Award type:** 5
- **Project period:** 2007-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983685

## Citation

> US National Institutes of Health, RePORTER application 9983685, Molecular control of tissue morphogenesis (5R01GM079340-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983685. Licensed CC0.

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