Actomyosin Pulsing in Tissue Integrity Maintenance during Morphogenesis

Abstract

The actomyosin cytoskeleton is responsible for many changes in cell and tissue shape. For a long time, the actomyosin cytoskeleton has been known to exhibit dynamic contractile behavior. Recently, discrete actomyosin assembly/disassembly cycles have also been observed in cells. These so-called actomyosin pulses have been observed in a variety of contexts, including cell polarization and division, and in epithelia, where they occur during tissue contraction, folding, and extension. In epithelia, evidence suggests that actomyosin pulsing, and more generally, actomyosin turnover, is required to maintain tissue integrity during contractile processes. This review explores possible functions for pulsing in the many instances during which pulsing has been observed, and also highlights proposed molecular mechanisms that drive pulsing.

Figure 1

A generalized schematic of actomyosin pulsing. Over the course of approximately one minute, Myo2 minifilaments assemble and contract an F-actin cytoskeletal network. This contraction can pull on cell adhesion receptors like adherens junctions or focal adhesions. Pulsed contraction is often followed by relaxation involving disassembly of Myo2 and the F-actin cytoskeleton.

Figure 2

Actomyosin turnover sustains intercellular actomyosin connectivity. (i) During epithelial morphogenesis, actomyosin pulses (dark red arrows) lead to contractions, (ii) contractility can disrupt intercellular actomyosin connections to adherens junctions (magenta asterisk). (iii) actomyosin turnover repairs these connections in wild-type cells, (iv) but with reduced turnover, tears appear in the epithelium between cells, interfering with morphogenesis.

Figure 3

Model for Myo2 and actin turnover in actomyosin pulses. Actomyosin pulse assembly occurs through a combination of RhoA activation via a RhoGEF, and actomyosin advection. Disassembly occurs through a combination of RhoA inactivation through a RhoGAP, and through dissociation of actomyosin from the apical actin cortex. The balance between assembly and disassembly is determined by the relative amount of RhoA activation/deactivation, or advection/dissociation. It is unclear whether disassembly is occurring at a constant rate (blue curve 1) or spikes after pulse assembly (blue curve 2).