# Role and regulation of the WAVE regulatory complex in epithelial morphogenesis

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2021 · $325,994

## Abstract

Project Summary
A central question in developmental biology is how biochemical signals and mechanical forces affect individual and
collective cell behaviors to control tissue morphogenesis. With advances in imaging technologies and image analysis tools
it is now possible to relate the dynamics of biochemical signals and force generating proteins with the deformation of cells
and tissue domains and measure the forces that power cellular and tissue remodeling. Using live imaging and quantitative
image analysis we discovered that contractile forces generated by contractile actomyosin networks affect cell shape
changes and tissue remodeling of the apical epithelium of the fly retina. Unexpectedly, we found that the WAVE regulatory
complex (WRC), the Arp2/3 complex and protrusive branched F-actin networks generate protrusive forces along apical
junctions that expand cell-cell contacts and resist the impact of contractile forces during tissue remodeling. The
mechanisms promoting protrusive dynamics at apical junctions during epithelial morphogenesis have been not
characterized. Therefore, the goal of the proposal is to bridge this gap in knowledge. In Specific Aim 1 we propose to
examine the role of the adhesion protein Sidekick in epithelial remodeling and the extent Sidekick physically targets the
WRC to apical junctions. In Specific Aim 2 we propose to examine the role phosophoinositide PI(3,4,5)3 and Pten in
epithelial tissue remodeling and the extent these components activate the WRC and coordinate protrusive with contractile
dynamics at apical junctions. Previous models suggested that maximizing adhesion between eye cell types controls eye
epithelial morphogenesis. Our data suggest that tensile forces with polarized distribution at apical junctions also play a
role. In Specific Aim 3 we propose to measure the tension that cell-cell contact hold using laser ablation and correlate
these measurements with the abundance of contractile MyoII and protrusive F-actin and with estimates of tension inferred
using an inverse Cellular Vertex Model utilizing segmented images. Additionally, we will use the same approach to
determine the relative contribution of the WRC and WRC regulators to the force balance. The completion of the Aims will
elucidate mechanisms by which protrusive WRC-Arp2/3-based F-actin networks operate at apical junctions and
coordinate with contractile actomyosin networks to control apical junctions remodeling, cellular morphogenesis and tissue
remodeling.

## Key facts

- **NIH application ID:** 10169463
- **Project number:** 5R01GM129151-04
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** VICTOR HATINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,994
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169463

## Citation

> US National Institutes of Health, RePORTER application 10169463, Role and regulation of the WAVE regulatory complex in epithelial morphogenesis (5R01GM129151-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169463. Licensed CC0.

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