A molecular logic of sensory coding revealed by optical tagging of physiologically-defined neuronal types

Lee, Donghoon; Kume, Maiko; Holy, Timothy E.

doi:10.1101/692079

Cited by 3 publications

(8 citation statements)

References 39 publications

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“…1-4). Many of these VSNs showed sub-micromolar BA sensitivity, comparable to other steroid-sensitive VRs (Haga-Yamanaka et al, 2015;Lee et al, 2019).…”

Section: Discussion: Vsns Are Sensitive Selective Ba Detectorsmentioning

confidence: 60%

“…4C, Clusters 3-15), and identified many previously-studied sulfated steroid-tuned VSN subpopulations (Fig. 4C, Clusters 16-21) (Lee et al, 2019;Meeks et al, 2010;Turaga and Holy, 2012;Xu et al, 2016). Also noteworthy were Clusters 6, 7, 11, and 14, which showed some degree of co-activation by BAs and sulfated steroid ligands.…”

Section: Vsns Shown Broad Responses To Bile Acids and Sulfated Steroidsmentioning

confidence: 62%

“…Previous studies have determined that steroid-sensitive VSNs express members of the V1R subfamily, which happen to project axons selectively to the anterior subregion of the AOB (Haga-Yamanaka et al, 2014;Isogai et al, 2011;Lee et al, 2019;Meeks et al, 2010). Based on the superficial chemical similarities between BAs and other steroids, and the partial overlap seen between BA-and sulfated steroid responsive VSNs, we hypothesized that V1Rs are likely serving as BA receptors.…”

Section: Vsns Shown Broad Responses To Bile Acids and Sulfated Steroidsmentioning

confidence: 99%

“…However, efforts to generate large-scale VR screening assays via heterologous expression has, for the most part, been unsuccessful (though see (Dey et al, 2013)). Other efforts have explored VNO ligand-receptor interactions using various approaches (Haga-Yamanaka et al, 2015;Isogai et al, 2011;Lee et al, 2019;Stein et al, 2016). Despite recent progress, a small fraction of the VR family has confirmed ligands (Haga-Yamanaka et al, 2014;Haga et al, 2010;Isogai et al, 2011;Isogai et al, 2018;Lee et al, 2019;Osakada et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…BAs are steroids that are structurally similar to other potent AOS ligands including sulfated and carboxylated glucocorticoids (Fu et al, 2015;Nodari et al, 2008). Despite evidence that many VSNs show selectivity for BAs compared to these other steroids, and evidence that some VRs are exquisitely sensitive to other steroids (Fu et al, 2015;Haga-Yamanaka et al, 2015;Isogai et al, 2011;Lee et al, 2019), questions remain about whether there are BA specialist VRs or whether BAs nonselectively activate certain steroid-sensitive VRs.…”

Section: Introductionmentioning

confidence: 99%

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Physiology-forward identification of bile acid sensitive vomeronasal receptors

Wong

Cao

Zhang

et al. 2019

Preprint

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The mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca 2+ imaging. These experiments revealed both broadly and narrowly tuned populations of BA-receptive VSNs with sub-micromolar sensitivities. We then developed a new physiology-forward approach for identifying AOS ligand-receptor interactions, which we call Fluorescence Live Imaging for Cell Capture and RNA-seq, or FLICCR-seq. FLICCR-seq analysis revealed 5 specific V1R-family receptors enriched in BA-sensitive VSNs. These studies introduce a powerful new approach for ligand-receptor matching and reveal biological mechanisms underlying mammalian BA chemosensation. Introduction:Chemosensory systems extract salient information from environmental cues that are critical for social and reproductive behaviors. In mice and other terrestrial mammals, the accessory olfactory system (AOS) guides innate behaviors such as territorial aggression and mating (Dulac and Torello, 2003;Keller et al., 2009). The initial detection of olfactory stimuli in the AOS is mediated by vomeronasal sensory neurons (VSNs), located in the vomeronasal organ (VNO), before these signals are routed to the accessory olfactory bulb and then behaviorally important regions including the medial amygdala and bed nucleus of the stria terminalis.Though the behavioral impacts of AOS chemosensation are manifold, our knowledge of the full complement of natural ligands for VSNs remains incomplete. Natural AOS ligands are found in the excretions of conspecific and heterospecific animals (e.g., urine, feces, tears, and saliva). These natural ligands include, but are not limited to, polar steroids, bile acids, major urinary proteins, and major histocompatibility complex peptide ligands (Chamero et al., 2007;Doyle et al., 2016;Leinders-Zufall et al., 2004;Nodari et al., 2008). As we learn more about the full natural complement of AOS ligands, new questions are arising about how these cues are detected by specific types of VSNs. Such knowledge is critical as we seek to understand how patterns of VSN activation by complex blends of environmental chemosignals cause changes in animal physiology and behavior.A major barrier preventing a deeper understanding of AOS function is a lack of ligandreceptor matches for AOS cues. VSNs generally express just one or two of ~300 unique vomeronasal receptors (VRs) or formyl peptide receptors (Dulac and Torello, 2003;Martini et al., 2001). The largely monoallelic expression of individual VRs by VSNs means that each VSN takes on the chemosensory sensitivity (or "tuning") of the dominantly expressed receptor. In theory, this feature wou...

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“…1-4). Many of these VSNs showed sub-micromolar BA sensitivity, comparable to other steroid-sensitive VRs (Haga-Yamanaka et al, 2015;Lee et al, 2019).…”

Section: Discussion: Vsns Are Sensitive Selective Ba Detectorsmentioning

confidence: 60%

Section: Vsns Shown Broad Responses To Bile Acids and Sulfated Steroidsmentioning

confidence: 62%

Section: Vsns Shown Broad Responses To Bile Acids and Sulfated Steroidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Physiology-forward identification of bile acid sensitive vomeronasal receptors

Wong

Cao

Zhang

et al. 2019

Preprint

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Whole-body integration of gene expression and single-cell morphology

Vergara

Pape

Meechan

et al. 2021

Cell

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Whole-body integration of gene expression and single-cell morphology

Vergara

Pape

Meechan

et al. 2020

Preprint

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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...

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A molecular logic of sensory coding revealed by optical tagging of physiologically-defined neuronal types

Cited by 3 publications

References 39 publications

Physiology-forward identification of bile acid sensitive vomeronasal receptors

Physiology-forward identification of bile acid sensitive vomeronasal receptors

Whole-body integration of gene expression and single-cell morphology

Whole-body integration of gene expression and single-cell morphology

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