# The dual role of the extracellular matrix in inter-tissue adhesion and tissue movement

> **NIH NIH F32** · YALE UNIVERSITY · 2022 · $67,582

## Abstract

Project Summary
The overall goal of the proposal is to determine how the extracellular matrix (ECM) contributes to the
morphogenesis of a three-dimensional tissue in vivo. The ECM is well studied in the field of cell migration;
however, limited examples exist analyzing the role of the ECM in other developmental contexts. To understand
the role of the ECM during development, a three-dimensional system in which the ECM can be tracked,
quantified, and manipulated in vivo during development is needed. The elongating neural tube in zebrafish is
well-suited to examine the ECM during three-dimensional tissue morphogenesis, due to the ease of imaging,
the ability to quantify Fibronectin matrix remodeling, and the numerous mutants and tools that are available in
zebrafish to manipulate the Fibronectin matrix and tissue mechanics. In this system, Fibronectin is present
between two tissues, the presomitic mesoderm (PSM) and neural tube. Fibronectin acts as a glue to hold the
two tissues together and is required for proper neural tube convergence along the medio-lateral axis. However,
the neural tube also moves posteriorly in relation to the PSM and Fibronectin matrix. When the main integrin
receptor that binds cells to the Fibronectin matrix is removed, no significant changes in cell motion are
observed in the neural tube. Furthermore, when Fibronectin is removed, the neural tube elongates fully.
Together these data indicate that cell migration along the Fibronectin matrix is not required for posterior
movement of the neural tube. Overall, this indicates that the neural tube moves past the PSM through a
mechanism other than cell migration along the Fibronectin matrix while also maintaining adhesion to the
Fibronectin matrix. One model for how this might occur is through changes in integrin dynamics in the neural
tube, in which decreases in integrin activation and stability could allow for tissue level motion while still
maintaining adhesion. In aim 1, I will investigate integrin binding dynamics in the context of posterior
motion of the neural tube. Using techniques, including FRET/FLIM, antibody staining, and live imaging, a
cross-scale view of integrin dynamics will be generated. These data will generate new hypotheses for how
integrins contribute to neural tube motion which will be tested using mutations that affect posterior motion of
the neural tube and mutations that strengthen or weaken integrin binding activity. In aim 2, I will determine
how adhesion of neural tube cells to the ECM influences their cell motion. This will be completed using
live tracking of Fibronectin matrix remodeling and cell motion in relation to their position to the Fibronectin
matrix. This data will generate hypotheses for how cell-cell and cell-ECM contacts influence cell behavior,
which will be further tested using established mutations that affect neural tube convergence and by altering cell
adhesion and cell contractility.

## Key facts

- **NIH application ID:** 10386517
- **Project number:** 1F32GM145094-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Sarah Jacquelyn Smith
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386517

## Citation

> US National Institutes of Health, RePORTER application 10386517, The dual role of the extracellular matrix in inter-tissue adhesion and tissue movement (1F32GM145094-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10386517. Licensed CC0.

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