Oligomerization and positive feedback on membrane recruitment encode dynamically stable PAR-3 asymmetries in the zygote.

Studies of PAR polarity have emphasized a paradigm in which mutually antagonistic PAR proteins form complementary polar domains in response to transient cues. A growing body of work suggests that the oligomeric scaffold PAR-3 can form unipolar asymmetries without mutual antagonism, but how it does so is largely unknown. Here we combine single molecule analysis and modeling to show how the interplay of two positive feedback loops promote dynamically stable unipolar PAR-3 asymmetries in early embryos.

Oligomerization of peripheral membrane proteins provides tunable control of cell surface polarity.

Asymmetric distributions of peripheral membrane proteins define cell polarity across all kingdoms of life. Non-linear positive feedback on membrane binding is essential to amplify and stabilize these asymmetries, but how specific molecular sources of non-linearity shape polarization dynamics remains poorly understood. Here we show that the ability to oligomerize, which is common to many peripheral membrane proteins, can play a profound role in shaping polarization dynamics in simple feedback circuits.

Pulsatile contractions and pattern formation in excitable actomyosin cortex.

The actin cortex is an active adaptive material, embedded with complex regulatory networks that can sense, generate, and transmit mechanical forces. The cortex exhibits a wide range of dynamic behaviours, from generating pulsatory contractions and travelling waves to forming organised structures. Despite the progress in characterising the biochemical and mechanical components of the actin cortex, the emergent dynamics of this mechanochemical system is poorly understood.

Modulating RhoA effectors induces transitions to oscillatory and more wavelike RhoA dynamics in zygotes.

Pulsatile RhoA dynamics underlie a wide range of cell and tissue behaviors. The circuits that produce these dynamics in different cells share common architectures based on fast positive and delayed negative feedback through F-actin, but they can produce very different spatiotemporal patterns of RhoA activity. However, the underlying causes of this variation remain poorly understood.

Filament-guided filament assembly provides structural memory of filament alignment during cytokinesis.

During cytokinesis, animal cells rapidly remodel the equatorial cortex to build an aligned array of actin filaments called the contractile ring. Local reorientation of filaments by active equatorial compression is thought to underlie the emergence of filament alignment during ring assembly. Here, combining single molecule analysis and modeling in one-cell C.

Actin bundle architecture and mechanics regulate myosin II force generation.

The actin cytoskeleton is a soft, structural material that underlies biological processes such as cell division, motility, and cargo transport. The cross-linked actin filaments self-organize into a myriad of architectures, from disordered meshworks to ordered bundles, which are hypothesized to control the actomyosin force generation that regulates cell migration, shape, and adhesion. Here, we use fluorescence microscopy and simulations to investigate how actin bundle architectures with varying polarity, spacing, and rigidity impact myosin II dynamics and force generation.

Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division.

Global tissue tension anisotropy has been shown to trigger stereotypical cell division orientation by elongating mitotic cells along the main tension axis. Yet, how tissue tension elongates mitotic cells despite those cells undergoing mitotic rounding (MR) by globally upregulating cortical actomyosin tension remains unclear. We addressed this question by taking advantage of ascidian embryos, consisting of a small number of interphasic and mitotic blastomeres and displaying an invariant division pattern.

The Dynamics of P Granule Liquid Droplets Are Regulated by the Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle.

P granules are phase-separated liquid droplets that play important roles in the maintenance of germ cell fate in Both the localization and formation of P granules are highly dynamic, but mechanisms that regulate such processes remain poorly understood. Here, we show evidence that the VASA-like germline RNA helicase GLH-1 couples distinct steps of its ATPase hydrolysis cycle to control the formation and disassembly of P granules. In addition, we found that the phenylalanine-glycine-glycine repeats in GLH-1 promote its localization at the perinucleus.

RhoA Mediates Epithelial Cell Shape Changes via Mechanosensitive Endocytosis.

Epithelial remodeling involves ratcheting behavior whereby periodic contractility produces transient changes in cell-cell contact lengths, which stabilize to produce lasting morphogenetic changes. Pulsatile RhoA activity is thought to underlie morphogenetic ratchets, but how RhoA governs transient changes in junction length, and how these changes are rectified to produce irreversible deformation, remains poorly understood. Here, we use optogenetics to characterize responses to pulsatile RhoA in model epithelium.

Differential Expression of a Classic Cadherin Directs Tissue-Level Contractile Asymmetry during Neural Tube Closure.

Embryos control force generation at tissue boundaries, but how they do so remains poorly understood. Here we show how tissue-specific expression of the type II cadherin, Cadherin2, patterns actomyosin contractility along tissue boundaries to control zippering and neural tube closure in the basal chordate, Ciona robusta. Cadherin2 is differentially expressed and homotypically enriched in neural cells along the neural/epidermal (Ne/Epi) boundary, where RhoA and myosin are activated during zipper progression.

Mechanosensitive Junction Remodeling Promotes Robust Epithelial Morphogenesis.

Morphogenesis of epithelial tissues requires tight spatiotemporal coordination of cell shape changes. In vivo, many tissue-scale shape changes are driven by pulsatile contractions of intercellular junctions, which are rectified to produce irreversible deformations. The functional role of this pulsatory ratchet and its mechanistic basis remain unknown.

Anillin Puts RhoA in Touch with PIP2.

In this issue of Developmental Cell, Budnar and colleagues report how the scaffolding protein anillin uses cycles of transient binding interactions to enhance the residence time and signaling output of active RhoA to control actomyosin contractility at epithelial junctions and during cell division.

Excitable RhoA dynamics drive pulsed contractions in the early embryo.

Pulsed actomyosin contractility underlies diverse modes of tissue morphogenesis, but the underlying mechanisms remain poorly understood. Here, we combined quantitative imaging with genetic perturbations to identify a core mechanism for pulsed contractility in early embryos. We show that pulsed accumulation of actomyosin is governed by local control of assembly and disassembly downstream of RhoA.

Rapid diffusion-state switching underlies stable cytoplasmic gradients in the zygote.

Protein concentration gradients organize cells and tissues and commonly form through diffusion away from a local source of protein. Interestingly, during the asymmetric division of the zygote, the RNA-binding proteins MEX-5 and PIE-1 form opposing concentration gradients in the absence of a local source. In this study, we use near-total internal reflection fluorescence (TIRF) imaging and single-particle tracking to characterize the reaction/diffusion dynamics that maintain the MEX-5 and PIE-1 gradients.

Dynamic interplay of cell fate, polarity and force generation in ascidian embryos.

A fundamental challenge in developmental biology is to understand how forces produced by individual cells are patterned in space and time and then integrated to produce stereotyped changes in tissue-level or embryo-level morphology. Ascidians offer a unique opportunity to address this challenge by studying how small groups of cells collectively execute complex, but highly stereotyped morphogenetic movements. Here we highlight recent progress and open questions in the study of ascidian morphogenesis, emphasizing the dynamic interplay of cell fate determination, cellular force generation and tissue-level mechanics.

Filament turnover tunes both force generation and dissipation to control long-range flows in a model actomyosin cortex.

Actomyosin-based cortical flow is a fundamental engine for cellular morphogenesis. Cortical flows are generated by cross-linked networks of actin filaments and myosin motors, in which active stress produced by motor activity is opposed by passive resistance to network deformation. Continuous flow requires local remodeling through crosslink unbinding and and/or filament disassembly.

The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity.

PAR proteins constitute a highly conserved network of scaffolding proteins, adaptors and enzymes that form and stabilize cortical asymmetries in response to diverse inputs. They function throughout development and across the metazoa to regulate cell polarity. In recent years, traditional approaches to identifying and characterizing molecular players and interactions in the PAR network have begun to merge with biophysical, theoretical and computational efforts to understand the network as a pattern-forming biochemical circuit.

Protein Clustering Shapes Polarity Protein Gradients.

In this issue of Developmental Cell, Dickinson et al. (2017) and Rodriguez et al. (2017), along with Wang et al.

Dynamic Opposition of Clustered Proteins Stabilizes Cortical Polarity in the C. elegans Zygote.

Dynamic maintenance of cell polarity is essential for development and physiology. Here we combine experiments and modeling to elucidate mechanisms that maintain cortical polarity in the C. elegans zygote.

A self-organized biomechanical network drives shape changes during tissue morphogenesis.

Tissue morphogenesis is orchestrated by cell shape changes. Forces required to power these changes are generated by non-muscle myosin II (MyoII) motor proteins pulling filamentous actin (F-actin). Actomyosin networks undergo cycles of assembly and disassembly (pulses) to cause cell deformations alternating with steps of stabilization to result in irreversible shape changes.

Isoforms Confer Characteristic Force Generation and Mechanosensation by Myosin II Filaments.

Myosin II isoforms with varying mechanochemistry and filament size interact with filamentous actin (F-actin) arrays to generate contractile forces in muscle and nonmuscle cells. How myosin II force production is shaped by isoform-specific motor properties and environmental stiffness remains poorly understood. Here, we used computer simulations to analyze force production by an ensemble of myosin motors against an elastically tethered actin filament.

Sequential contraction and exchange of apical junctions drives zippering and neural tube closure in a simple chordate.

Unidirectional zippering is a key step in neural tube closure that remains poorly understood. Here, we combine experimental and computational approaches to identify the mechanism for zippering in a basal chordate, Ciona intestinalis. We show that myosin II is activated sequentially from posterior to anterior along the neural/epidermal (Ne/Epi) boundary just ahead of the advancing zipper.