Path integration is a widespread navigational strategy in which directional changes and distance covered are continuously integrated on an outward journey, enabling a straight-line return to home. Bees use vision for this task-a celestial-cue-based visual compass and an optic-flow-based visual odometer-but the underlying neural integration mechanisms are unknown. Using intracellular electrophysiology, we show that polarized-light-based compass neurons and optic-flow-based speed-encoding neurons converge in the central complex of the bee brain, and through block-face electron microscopy, we identify potential integrator cells. Based on plausible output targets for these cells, we propose a complete circuit for path integration and steering in the central complex, with anatomically identified neurons suggested for each processing step. The resulting model circuit is thus fully constrained biologically and provides a functional interpretation for many previously unexplained architectural features of the central complex. Moreover, we show that the receptive fields of the newly discovered speed neurons can support path integration for the holonomic motion (i.e., a ground velocity that is not precisely aligned with body orientation) typical of bee flight, a feature not captured in any previously proposed model of path integration. In a broader context, the model circuit presented provides a general mechanism for producing steering signals by comparing current and desired headings-suggesting a more basic function for central complex connectivity, from which path integration may have evolved.

Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.

Pathogenesis induced by SARS-CoV-2 is thought to result from both an inflammation dominated cytokine response and virus-induced cell perturbation causing cell death. Here, we employ an integrative imaging analysis to determine morphological organelle alterations induced in SARS-CoV-2 infected human lung epithelial cells. We report 3D electron microscopy reconstructions of whole-cells and subcellular compartments, revealing extensive fragmentation of the Golgi apparatus, alteration of the mitochondrial network and recruitment of peroxisomes to viral replication organelles formed by clusters of double-membrane vesicles (DMVs). These are tethered to the endoplasmic reticulum, providing insights into DMV biogenesis and spatial coordination of SARS-CoV-2 replication. Live cell imaging combined with an infection sensor reveals profound remodeling of cytoskeleton elements. Pharmacological inhibition of their dynamics suppresses SARS-CoV-2 replication. We thus report insights into virus-induced cytopathic effects, and provide alongside a comprehensive publicly available repository of 3D data-sets of SARS-CoV-2 infected cells for download and smooth online visualization.

The structural organisation of pancreatic β-cells in the islets of Langerhans is relatively unknown. Here, using three-dimensional (3D) two-photon, 3D confocal and 3D block-face serial electron microscopy, we demonstrate a consistent in situ polarisation of β-cells and define three distinct cell surface domains. An apical domain located at the vascular apogee of β-cells, defined by the location of PAR-3 (also known as PARD3) and ZO-1 (also known as TJP1), delineates an extracellular space into which adjacent β-cells project their primary cilia. A separate lateral domain, is enriched in scribble and Dlg, and colocalises with E-cadherin and GLUT2 (also known as SLC2A2). Finally, a distinct basal domain, where the β-cells contact the islet vasculature, is enriched in synaptic scaffold proteins such as liprin. This 3D analysis of β-cells within intact islets, and the definition of distinct domains, provides new insights into understanding β-cell structure and function.

The centrosome is the primary microtubule-organizing center (MTOC) of most animal cells; however, this organelle is absent during early mammalian development. Therefore, the mechanism by which the mammalian embryo organizes its microtubules (MTs) is unclear. We visualize MT bridges connecting pairs of cells and show that the cytokinetic bridge does not undergo stereotypical abscission after cell division. Instead, it serves as scaffold for the accumulation of the MT minus-end-stabilizing protein CAMSAP3 throughout interphase, thereby transforming this structure into a noncentrosomal MTOC. Transport of the cell adhesion molecule E-cadherin to the membrane is coordinated by this MTOC and is required to form the pluripotent inner mass. Our study reveals a noncentrosomal form of MT organization that directs intracellular transport and is essential for mammalian development.

Deep-sea fishes evolved an unconventional visual system to optimize vision in twilight conditions.

Highlights d Caveolae influence contractile tension in epithelial monolayers d Caveolin-1 depletion enhances epithelial tension via PtdIns(4,5)P 2 signaling d Elevated epithelial tension inhibits oncogenic cell extrusion

Animal bodies are composed of hundreds of cell types that differ in location, morphology, cytoarchitecture, and physiology. This is reflected by cell type-specific transcription factors and downstream effector genes implementing functional specialisation. Here, we establish and explore the link between cell type-specific gene expression and subcellular morphology for the entire body of the marine annelid Platynereis dumerilii. For this, we registered a whole-body cellular expression atlas to a high-resolution electron microscopy dataset, automatically segmented all cell somata and nuclei, and clustered the cells according to gene expression or morphological parameters. We show that collective gene expression most efficiently identifies spatially coherent groups of cells that match anatomical boundaries, which indicates that combinations of regionally expressed transcription factors specify tissue identity. We provide an integrated browser as a Fiji plugin to readily explore, analyse and visualise multimodal datasets with remote ondemand access to all available datasets. Figure 1: Ultrastructure of a whole Platynereis by serial block-face scanning electron microscopy.A: The 3D SBEM dataset can be observed in multiple orientations, either along the acquisition plane (transversal plane, top row) or as orthogonal projections (horizontal plane, bottom row; scale bar: 50 µm). B-E: fine ultrastructure is revealed when exploring the datasets at native resolution (10 nm pixel-size x/y; scale bars: 2 µm). B: epithelial cell, interfacing the cuticle and the underlying muscle. Bundles of cytoskeletal filaments (arrowhead) form part of the attachment complex (inset). C: the adult eye forms a pigment cup composed of pigment cells (PiC) and rhabdomeric photoreceptors (rPRC). The photoreceptors extend a distal segment made by microvillar projections (mi) for light detection. In the centre of the pigment cup is the vitreous body (vb). D: longitudinal muscle fibres are cut transversally displaying cross-sections of the sarcomere as well as of the sarcoplasmic reticulum that contacts the plasma membrane (inset). E: cross section of the distal part of the nephridia, highlighting the autocell junction (arrow) which forms a lumen. The lumen houses a bundle of motile cilia (identified by the 9+2 microtubule arrangement, inset), which are contributed by each cell of the nephridium, noted by the presence of basal bodies. Panels B to E are snapshots selected from the full volume and can be retrieved directly from the PlatyBrowser "Bookmark" function. Supplementary Figure 2A). Figure 2 gives a few examples of the achieved segmentation quality for epidermal cells (B), muscles (C) and nephridia (D). We measured nuclei sizes to range from 33.6 to 147.5 cubic microns, and cell sizes from 59.8 to 1224.6 cubic microns. Note that neurites in the neuropil have not been segmented, as they are not sufficiently preserved in the EM volume for automated segmentation. Figure 2: Segmentation of nuclei, cells, tissues and body parts.A. Cells and nuclei ar...