# Dynamic control of actin network architecture in early C. elegans embryos

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $473,354

## Abstract

Project Abstract/Summary
 Cells utilize an array of actin binding proteins with diverse and complementary properties to
assemble, maintain and disassemble a range of distinct F-actin networks to facilitate different
fundamental functions including motility, polarization and division. To serve its function, each of these
networks has a unique architecture defined by the number, lengths and connectivity of its filaments,
which is maintained by a continuous dynamical balance of actin filament assembly, remodeling and
disassembly. A fundamental challenge is to understand how functional network architectures are formed
and maintained by the continuous coupling of architecture and assembly dynamics. Here we are
focusing on the cell cortex, a dynamic network of actin filaments, crosslinkers and myosin motors, lying
just beneath the plasma membrane, that undergoes rapid deformation and flow to drive cell movement,
polarization, division and tissue morphogenesis. How ensembles of actin regulatory factors work in
concert to simultaneously regulate actin filament network architecture assembly and dynamics at the
cortex of living cells is poorly understood. The one cell C. elegans embryo provides a uniquely powerful
opportunity to address these questions in a single large cell, that is directly accessible to high resolution
microscopy, with powerful genetics, transgenics, CRISPR and RNAi. The C. elegans cortex is primarily
composed of an F-actin network of linear filaments and small filament bundles that are assembled by
formin CYK-1-mediated polymerization of profilin-actin, and decorated by actin filament crosslinkers
plastin PLST-1, anillin ANI-1, and by mini-filaments of non-muscle myosin II NMY-2. Conversely, cofilin
UNC-60A and capping protein CAP-1/CAP-2 appear to be key regulators of filament disassembly and
filament length, respectively.
 We are addressing how the C. elegans cortical F-actin network architecture is formed and
maintained through the dynamic integration of formin-dependent filament assembly, filament
crosslinking, filament capping, and cofilin-dependent filament disassembly, all while the network
experiences continuous myosin-driven deformation and flow. We are combining the complementary
state-of-the-art in vivo expertise (quantitative single molecule imaging and particle analysis) and in vitro
expertise (reconstitution and biophysical analysis) of the Ed Munro and David Kovar lab's to address two
major questions concerning the architecture and dynamics of the C. elegans F-actin cortex. First, we will
characterize the fundamental dynamics, regulation and feedback control of formin-mediated actin
filament and bundle assembly (Aim 1). Second, we will investigate the fundamental dynamics, regulation
and feedback control of cofilin-mediated actin filament disassembly of the formin actin filament networks
(Aim 2).

## Key facts

- **NIH application ID:** 10280989
- **Project number:** 1R01GM143576-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** David R Kovar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $473,354
- **Award type:** 1
- **Project period:** 2021-08-04 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10280989

## Citation

> US National Institutes of Health, RePORTER application 10280989, Dynamic control of actin network architecture in early C. elegans embryos (1R01GM143576-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10280989. Licensed CC0.

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