Cross-linker-mediated regulation of actin network organization controls tissue morphogenesis.

Daniel Krueger,Theresa Quinkler,Carsten Sachse,Stefano De Renzis,Simon Arnold Mortensen

doi:10.1083/jcb.201811127

Abstract

Contraction of cortical actomyosin networks driven by myosin activation controls cell shape changes and tissue morphogenesis during animal development. In vitro studies suggest that contractility also depends on the geometrical organization of actin filaments. Here we analyze the function of actomyosin network topology in vivo using optogenetic stimulation of myosin-II in Drosophila embryos. We show that early during cellularization, hexagonally arrayed actomyosin fibers are resilient to myosin-II activation. Actomyosin fibers then acquire a ring-like conformation and become contractile and sensitive to myosin-II. This transition is controlled by Bottleneck, a Drosophila unique protein expressed for only a short time during early cellularization, which we show regulates actin bundling. In addition, it requires two opposing actin cross-linkers, Filamin and Fimbrin. Filamin acts synergistically with Bottleneck to facilitate hexagonal patterning, while Fimbrin controls remodeling of the hexagonal network into contractile rings. Thus, actin cross-linking regulates the spatio-temporal organization of actomyosin contraction in vivo, which is critical for tissue morphogenesis.

Highlights

1993) was shown to regulate this transition from hexagonal to circular array
Using purified proteins and purified actin, the author clearly demonstrate in this study that Bottleneck protein is sufficient to bundle actin filaments in vitro. They screen for actin regulators localized at the furrow and found that Cheerio and Fimbrin both localize to the basal actomyosin network
Using tools to downregulate Cheerio and Fimbrin proteins, they show very convincing experiments that establish the epistatic relationship between Bottleneck, Fimbrin and Cheerio : while Cheerio and Bottleneck are required to prevent early constriction, Fimbrin promotes the transition to a contractile network

Summary

Introduction

1993) was shown to regulate this transition from hexagonal to circular array. Bottleneck mutants show premature constriction and premature reorganization of the cytoskeleton, and Bottleneck protein disappears from the furrow at the onset of the fast phase (Schejter and Wieshauss 1993).

Results

Conclusion