# Regulation of dynamic actin networks during epithelial morphogenesis

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $555,696

## Abstract

Project Summary
Embryonic development requires the dynamic remodeling of epithelial sheets as the embryo
transforms itself during morphogenesis. Understanding these events has important implications
for understanding common human birth defects and common cancers. Our aim is a
multidisciplinary, integrated analysis of morphogenetic movements in embryos that unites
detailed structural analysis, single-molecule biophysics, genetics, and dynamic in vivo analysis,
using the C. elegans embryo as a model system. Our recent focus has been in two broad areas
of cytoskeletal regulation: the mechanisms by which mechanotransduction occurs through the
cadherin/catenin complex during morphogenesis, and cellular mechanisms of epithelial cell
rearrangement driven by basolateral motility. We will continue these emphases here:
1. Define mechanisms of α-catenin mechanotransduction during morphogenesis: We
 will examine the tension-dependent interaction of SRGP-1/srGAP with HMP-1/α-catenin and
 how SRGP-1 recruitment positively modulates cadherin complex function.
2. Define mechanisms of self-healing of junctional actin networks under tension during
 morphogenesis: We will test a model in which different LIM-domain containing repeat
 (LCR) proteins stabilize different substructures with the junctional proximal F-actin network
 under tension to prevent self-injury.
3. Define mechanisms of local actin polymerization in during epithelial cell
 rearrangement: We will use an integrated approach to determine how CRML-1/CARMIL
 negatively regulates motility via effects on the barbed end actin capping machinery.
4. Define local signaling pathways that promote polarized motility during cell
 rearrangement: We will determine how additional signaling components regulate epithelial
 cell rearrangement.
As a result of these studies, we will gain new insight into how adherens junctions are able to
withstand and respond to tension in a living organism, and we will elucidate a novel pathway
regulating cell intercalation via basolateral protrusive activity. Each project has widespread
implications for understanding processes crucial for diverse cellular events during human
development and disease.

## Key facts

- **NIH application ID:** 10406751
- **Project number:** 1R35GM145312-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jeffrey D Hardin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $555,696
- **Award type:** 1
- **Project period:** 2022-05-13 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406751

## Citation

> US National Institutes of Health, RePORTER application 10406751, Regulation of dynamic actin networks during epithelial morphogenesis (1R35GM145312-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10406751. Licensed CC0.

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