Publications by authors named "Sally Horne-Badovinac"

The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored.

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Migrating epithelial cells globally align their migration machinery to achieve tissue-level movement. Biochemical signaling across leading-trailing cell-cell interfaces can promote this alignment by partitioning migratory behaviors like protrusion and retraction to opposite sides of the interface. However, how signaling proteins become organized at interfaces to accomplish this is poorly understood.

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Migrating epithelial cells globally align their migration machinery to achieve tissue-level movement. Biochemical signaling across leading-trailing cell-cell interfaces can promote this alignment by partitioning migratory behaviors like protrusion and retraction to opposite sides of the interface. However, how the necessary signaling proteins become organized at this site is poorly understood.

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The Drosophila egg chamber is a powerful system to study epithelial cell collective migration and polarized basement membrane secretion. A strength of this system is the ability to capture these dynamic processes in ex vivo organ culture using high-resolution live imaging. Ex vivo culture also allows acute pharmacological or labeling treatments, extending the versatility of the system.

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The follicular epithelial cells of the Drosophila egg chamber have become a premier model to study how cells globally orient their actin-based machinery for collective migration. The basal surface of each follicle cell has lamellipodial and filopodial protrusions that extend from its leading edge and an array of stress fibers that mediate its adhesion to the extracellular matrix; these migratory structures are all globally aligned in the direction of tissue movement. To understand how this global alignment is achieved, one must be able to reliably visualize the underlying F-actin; however, dynamic F-actin networks can be difficult to preserve in fixed tissues.

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Article Synopsis
  • Cells in a group must align their migratory machinery for coordinated movement, a process called collective migration, which is essential in animal development.
  • The study focuses on follicular epithelial cells, revealing that the protein Fat2 plays a crucial role by localizing to the back of each cell and enhancing F-actin-rich protrusions at the front of the adjacent cell.
  • Fat2 stabilizes the distribution of the WAVE complex at the leading edge, promoting consistent protrusive activity and ensuring that all cells work together efficiently during migration.
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Epithelial tissues are lined with a sheet-like basement membrane (BM) extracellular matrix at their basal surfaces that plays essential roles in adhesion and signaling. BMs also provide mechanical support to guide morphogenesis. Despite their importance, we know little about how epithelial cells secrete and assemble BMs during development.

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Stress fibers (SFs) are actomyosin bundles commonly found in individually migrating cells in culture. However, whether and how cells use SFs to migrate in vivo or collectively is largely unknown. Studying the collective migration of the follicular epithelial cells in , we found that the SFs in these cells show a novel treadmilling behavior that allows them to persist as the cells migrate over multiple cell lengths.

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Membrane traffic can be studied by imaging a cargo protein as it transits the secretory pathway. The best tools for this purpose initially block export of the secretory cargo from the endoplasmic reticulum (ER) and then release the block to generate a cargo wave. However, previously developed regulatable secretory cargoes are often tricky to use or specific for a single model organism.

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Dynamic rearrangements of epithelial cells play central roles in shaping tissues and organs during development. There are also scenarios, however, in which epithelial cell movements synergize with the secretion of extracellular matrix to build rigid, acellular structures that persist long after the cells are gone. The formation of the micropyle provides an elegant example of this epithelial craftsmanship.

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How a basement membrane continuously surrounds an organ that is growing and changing shape is not yet understood. In this issue of Developmental Cell, Matsubayashi et al. and Keeley et al.

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How extracellular matrix contributes to tissue morphogenesis is still an open question. In the ovarian follicle, it has been proposed that after Fat2-dependent planar polarization of the follicle cell basal domain, oriented basement membrane (BM) fibrils and F-actin stress fibers constrain follicle growth, promoting its axial elongation. However, the relationship between BM fibrils and stress fibers and their respective impact on elongation are unclear.

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The extracellular matrix (ECM) is an assembly of hundreds of proteins that structurally supports the cells it surrounds and biochemically regulates their functions. has emerged as a powerful model organism to study fundamental mechanisms underlying ECM protein secretion, ECM assembly, and ECM roles in pathophysiological processes. However, as of today, we do not possess a well-defined list of the components forming the ECM of this organism.

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How biochemical and mechanical information are integrated during tissue development is a central question in morphogenesis. In many biological systems, the PIX-GIT complex localises to focal adhesions and integrates both physical and chemical information. We used Drosophila melanogaster egg chamber formation to study the function of PIX and GIT orthologues (dPix and Git, respectively), and discovered a central role for this complex in controlling myosin activity and epithelial monolayering.

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Collective migration of epithelial cells is essential for morphogenesis, wound repair, and the spread of many cancers, yet how individual cells signal to one another to coordinate their movements is largely unknown. Here, we introduce a tissue-autonomous paradigm for semaphorin-based regulation of collective cell migration. Semaphorins typically regulate the motility of neuronal growth cones and other migrating cell types by acting as repulsive cues within the migratory environment.

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A new study upends the clear distinction between cell-cell adhesion and cell-matrix adhesion by showing that type IV collagen is essential for inter-adipocyte adhesion in the Drosophila fat body.

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When cells migrate through the body, their motility is continually influenced by interactions with other cells. The Fat-like cadherins are cell-cell signaling proteins that promote migration in multiple cell types. Recent studies suggest, however, that Fat-like cadherins influence motility differently in mammals versus Drosophila, with the cadherin acting at the leading edge of mammalian cells and the trailing edge of Drosophila cells.

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Collective migration of epithelial cells underlies diverse tissue-remodeling events, but the mechanisms that coordinate individual cell migratory behaviors for collective movement are largely unknown. Studying the Drosophila follicular epithelium, we show that the cadherin Fat2 and the receptor tyrosine phosphatase Lar function in a planar signaling system that coordinates leading and trailing edge dynamics between neighboring cells. Fat2 signals from each cell's trailing edge to induce leading edge protrusions in the cell behind, in part by stabilizing Lar's localization in these cells.

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Drosophila egg chamber development depends on a number of dynamic cellular processes that contribute to the final shape and function of the egg. We can gain insight into the mechanisms underlying these events by combining the power of Drosophila genetics and ex vivo live imaging. During developmental stages 1-8, egg chambers rotate around their anterior-posterior axes due to collective migration of the follicular epithelium.

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Basement membranes (BMs) are planar protein networks that support epithelial function. Regulated changes to BM architecture can also contribute to tissue morphogenesis, but how epithelia dynamically remodel their BMs is unknown. In Drosophila, elongation of the initially spherical egg chamber correlates with the generation of a polarized network of fibrils in its surrounding BM.

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Organs are formed from multiple cell types that make distinct contributions to their shape. The Drosophila egg chamber provides a tractable model to dissect such contributions during morphogenesis. Egg chambers consist of 16 germ cells (GCs) surrounded by a somatic epithelium.

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Basement membranes (BMs) are sheetlike extracellular matrices found at the basal surfaces of epithelial tissues. The structural and functional diversity of these matrices within the body endows them with the ability to affect multiple aspects of cell behavior and communication; for this reason, BMs are integral to many developmental processes. The power of Drosophila genetics, as applied to the BM, has yielded substantial insight into how these matrices influence development.

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Basement membranes (BMs) are sheet-like extracellular matrices that provide essential support to epithelial tissues. Recent evidence suggests that regulated changes in BM architecture can direct tissue morphogenesis, but the mechanisms by which cells remodel BMs are largely unknown. The Drosophila egg chamber is an organ-like structure that transforms from a spherical to an ellipsoidal shape as it matures.

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Horne-Badovinac tracks how coordinated cellular movements mold tissues.

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