# The Molecular Biophysics and Tissue Biomechanics of Somite Morphogenesis

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $383,588

## Abstract

Reciprocal regulation between the ECM and associated epithelial cells is integral to
development, homeostasis and disease. Somites are segmental precursors of the vertebral
column and musculature that form via a mesenchymal to epithelial transition. Somite
morphogenesis is dependent upon a Fibronectin ECM, the Fibronectin receptor Integrin
51, the cell adhesion protein Cadherin 2 and bidirectional signaling via the receptor
tyrosine kinase EphA4 and its membrane bound ligand Ephrin-B2a. These genes/pathways
mediate cell-ECM adhesion, cell-cell adhesion and contact mediated cell repulsion, and our
hypothesis is that the physical organizing activity of the somite boundary emerges via
specific spatiotemporal intertwining of differential cell adhesion and ECM constrained cell
repulsion. In Aim 1, fluorescence correlation spectroscopy (FCS) and fluorescence
crosscorrelation spectroscopy (FCCS) will be used quantify protein diffusion and protein
binding constants in vivo. These experiments will determine whether the segregation of
these cell surface proteins occurs via diffusion and capture or active mobilization.
Additionally, the roles of integrin 5, cadherin 2 and ephrin-b2a in driving these changes in
subcellular localization will be elucidated by performing FCCS in live mutant embryos. In
Aim 2, a systems analysis of cell motion will be used to quantify tissue biomechanics during
somite morphogenesis in wild-type and mutant embryos. In Aim 3, we quantify the relative
levels of Integrin activation via cytoplasmic signals versus via positive feedback through the
ECM. Positive and negative feedback between biological mechanisms creates network effects
that are hard to predict a priori and difficult to fully explore experimentally. in silico modeling will
be used to systematically examine the relationships between cell adhesion, cell-ECM
adhesion and cell contact mediated repulsion in somite morphogenesis in order to help
interpret and prioritize more resource intensive wet-lab experiments.

## Key facts

- **NIH application ID:** 9896870
- **Project number:** 5R01GM127876-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** SCOTT A HOLLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,588
- **Award type:** 5
- **Project period:** 2018-04-13 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896870

## Citation

> US National Institutes of Health, RePORTER application 9896870, The Molecular Biophysics and Tissue Biomechanics of Somite Morphogenesis (5R01GM127876-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896870. Licensed CC0.

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