Surrounding tissue morphogenesis with disrupted posterior midgut invagination during Drosophila gastrulation.

Gastrulation involves multiple, physically-coupled tissue rearrangements. During Drosophila gastrulation, posterior midgut (PMG) invagination promotes both germband extension and hindgut invagination, but whether the normal epithelial rearrangement of PMG invagination is required for morphogenesis of the connected tissues has been unclear. In steppke mutants, epithelial organization of the PMG primordium is strongly disrupted.

Centrosome-organized plasma membrane infoldings linked to growth of a cortical actin domain.

Regulated cell shape change requires the induction of cortical cytoskeletal domains. Often, local changes to plasma membrane (PM) topography are involved. Centrosomes organize cortical domains and can affect PM topography by locally pulling the PM inward.

Confinement promotes nematic alignment of spindle-shaped cells during Drosophila embryogenesis.

Tissue morphogenesis is often controlled by actomyosin networks pulling on adherens junctions (AJs), but junctional myosin levels vary. At an extreme, the Drosophila embryo amnioserosa forms a horseshoe-shaped strip of aligned, spindle-shaped cells lacking junctional myosin. What are the bases of amnioserosal cell interactions and alignment? Compared with surrounding tissue, we find that amnioserosal AJ continuity has lesser dependence on α-catenin, the mediator of AJ-actomyosin association, and greater dependence on Bazooka/Par-3, a junction-associated scaffold protein.

Contractile and expansive actin networks in Drosophila: Developmental cell biology controlled by network polarization and higher-order interactions.

Actin networks are central to shaping and moving cells during animal development. Various spatial cues activate conserved signal transduction pathways to polarize actin network assembly at sub-cellular locations and to elicit specific physical changes. Actomyosin networks contract and Arp2/3 networks expand, and to affect whole cells and tissues they do so within higher-order systems.

SCAR/WAVE complex recruitment to a supracellular actomyosin cable by myosin activators and a junctional Arf-GEF during dorsal closure.

Expansive Arp2/3 actin networks and contractile actomyosin networks can be spatially and temporally segregated within the cell, but the networks also interact closely at various sites, including adherens junctions. However, molecular mechanisms coordinating these interactions remain unclear. We found that the SCAR/WAVE complex, an Arp2/3 activator, is enriched at adherens junctions of the leading edge actomyosin cable during dorsal closure.

Axis specification: Breaking symmetry with a myosin patch in the egg.

Drosophila anterior-posterior axis specification occurs in the oocyte, but the initial symmetry break has been unclear. A new study reveals that a posterior domain of cortical myosin is induced with unique post-translational modification and dynamics and that this domain recruits downstream posterior determinants.

Emergence of a smooth interface from growth of a dendritic network against a mechanosensitive contractile material.

Structures and machines require smoothening of raw materials. Self-organized smoothening guides cell and tissue morphogenesis and is relevant to advanced manufacturing. Across the syncytial embryo surface, smooth interfaces form between expanding Arp2/3-based actin caps and surrounding actomyosin networks, demarcating the circumferences of nascent dome-like compartments used for pseudocleavage.

The Arf-GEF Steppke promotes F-actin accumulation, cell protrusions and tissue sealing during Drosophila dorsal closure.

Cytohesin Arf-GEFs promote actin polymerization and protrusions of cultured cells, whereas the Drosophila cytohesin, Steppke, antagonizes actomyosin networks in several developmental contexts. To reconcile these findings, we analyzed epidermal leading edge actin networks during Drosophila embryo dorsal closure. Here, Steppke is required for F-actin of the actomyosin cable and for actin-based protrusions.

Arf-GEF localization and function at myosin-rich adherens junctions via coiled-coil heterodimerization with an adaptor protein.

Tissue dynamics require regulated interactions between adherens junctions and cytoskeletal networks. For example, myosin-rich adherens junctions recruit the cytohesin Arf-GEF Steppke, which down-regulates junctional tension and facilitates tissue stretching. We dissected this recruitment mechanism with structure-function and other analyses of Steppke and Stepping stone, an implicated adaptor protein.

Par-1 controls the composition and growth of cortical actin caps during embryo cleavage.

Cell structure depends on the cortex, a thin network of actin polymers and additional proteins underlying the plasma membrane. The cell polarity kinase Par-1 is required for cells to form following syncytial embryo development. This requirement stems from Par-1 promoting cortical actin caps that grow into dome-like metaphase compartments for dividing syncytial nuclei.

Apical polarity proteins recruit the RhoGEF Cysts to promote junctional myosin assembly.

The spatio-temporal regulation of small Rho GTPases is crucial for the dynamic stability of epithelial tissues. However, how RhoGTPase activity is controlled during development remains largely unknown. To explore the regulation of Rho GTPases in vivo, we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13.

Dynamics of PAR Proteins Explain the Oscillation and Ratcheting Mechanisms in Dorsal Closure.

We present a vertex-based model for Drosophila dorsal closure that predicts the mechanics of cell oscillation and contraction from the dynamics of the PAR proteins. Based on experimental observations of how aPKC, Par-6, and Bazooka translocate from the circumference of the apical surface to the medial domain, and how they interact with each other and ultimately regulate the apicomedial actomyosin, we formulate a system of differential equations that captures the key features of dorsal closure, including distinctive behaviors in its early, slow, and fast phases. The oscillation in cell area in the early phase of dorsal closure results from an intracellular negative feedback loop that involves myosin, an actomyosin regulator, aPKC, and Bazooka.

Collision of Expanding Actin Caps with Actomyosin Borders for Cortical Bending and Mitotic Rounding in a Syncytium.

The early Drosophila embryo is a large syncytial cell that compartmentalizes mitotic spindles with furrows. Before furrow ingression, an Arp2/3 actin cap forms above each nucleus and is encircled by actomyosin. We investigated how these networks transform a flat cortex into a honeycomb-like compartmental array.

Organizing Complex Tissue Architecture by Pushing and Pulling Cell Contacts.

Changes to cell shape and interaction drive animal tissue morphogenesis. Reporting now in Developmental Cell, Del Signore et al. (2018) describe active lengthening of cell-cell contacts by Arp2/3-based actin networks.

Protein clustering for cell polarity: Par-3 as a paradigm.

The scaffold protein Par-3 ( Bazooka) is a central organizer of cell polarity across animals. This review focuses on how the clustering of Par-3 contributes to cell polarity. It begins with the Par-3 homo-oligomerization mechanism and its regulation by Par-1 phosphorylation.

Sculpting epithelia with planar polarized actomyosin networks: Principles from Drosophila.

Drosophila research has revealed how planar polarized actomyosin networks affect various types of tissue morphogenesis. The networks are positioned by both tissue-wide patterning factors (including Even-skipped, Runt, Engrailed, Invected, Hedgehog, Notch, Wingless, Epidermal Growth Factor, Jun N-terminal kinase, Sex combs reduced and Fork head) and local receptor complexes (including Echinoid, Crumbs and Toll receptors). Networks with differing super-structure and contractile output have been discovered.

An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.

In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress.

Key roles of Arf small G proteins and biosynthetic trafficking for animal development.

Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development.

The Arf GAP Asap promotes Arf1 function at the Golgi for cleavage furrow biosynthesis in Drosophila.

Biosynthetic traffic from the Golgi drives plasma membrane growth. For Drosophila embryo cleavage, this growth is rapid but regulated for cycles of furrow ingression and regression. The highly conserved small G protein Arf1 organizes Golgi trafficking.

Cadherin Trafficking for Tissue Morphogenesis: Control and Consequences.

Cadherin-based adherens junctions are critical for connecting cells in tissues. Regulated cadherin trafficking also makes these complexes amazingly dynamic, with permissive and instructive consequences on multicellular development. Here, we review how cadherin trafficking affects various forms of tissue morphogenesis from Drosophila and Caenorhabditis elegans to zebrafish, Xenopus and mouse.

PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila.

The recruitment of GDP/GTP exchange factors (GEFs) to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear.

A Par-1-Par-3-Centrosome Cell Polarity Pathway and Its Tuning for Isotropic Cell Adhesion.

To form regulated barriers between body compartments, epithelial cells polarize into apical and basolateral domains and assemble adherens junctions (AJs). Despite close links with polarity networks that generate single polarized domains, AJs distribute isotropically around the cell circumference for adhesion with all neighboring cells [1-3]. How AJs avoid the influence of polarity networks to maintain their isotropy has been unclear.

Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair.

Embryonic epithelia have a remarkable ability to rapidly repair wounds. A supracellular actomyosin cable around the wound coordinates cellular movements and promotes wound closure. Actomyosin cable formation is accompanied by junctional rearrangements at the wound margin.