Complex Signaling System Research Articles

Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch.

How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination of Bone morphogenetic protein (Bmp), Endothelin-1 (Edn1), and Notch signaling, and this system is highly robust. We combine NanoString experiments of early D-V gene expression with live imaging of arch development in zebrafish to construct a computational model of the D-V mandibular patterning network. The model recapitulates published genetic perturbations in arch development. Patterning is most sensitive to changes in Bmp signaling, and the temporal order of gene expression modulates the response of the patterning network to noise. Thus, our integrated systems biology approach reveals non-intuitive features of the complex signaling system crucial for craniofacial development, including novel insights into roles of gene expression timing and stochasticity in signaling and gene regulation.

Suppressor mutations reveal an NtrC-like response regulator, NmpR, for modulation of Type-IV Pili-dependent motility in Myxococcus xanthus.

Two-component signaling systems (TCS) regulate bacterial responses to environmental signals through the process of protein phosphorylation. Specifically, sensor histidine kinases (SK) recognize signals and propagate the response via phosphorylation of a cognate response regulator (RR) that functions to initiate transcription of specific genes. Signaling within a single TCS is remarkably specific and cross-talk between TCS is limited. However, regulation of the flow of information through complex signaling networks that include closely related TCS remains largely unknown. Additionally, many bacteria utilize multi-component signaling networks which provide additional genetic and biochemical interactions that must be regulated for signaling fidelity, input and output specificity, and phosphorylation kinetics. Here we describe the characterization of an NtrC-like RR that participates in regulation of Type-IV pilus-dependent motility of Myxococcus xanthus and is thus named NmpR, NtrC Modulator of Pili Regulator. A complex multi-component signaling system including NmpR was revealed by suppressor mutations that restored motility to cells lacking PilR, an evolutionarily conserved RR required for expression of pilA encoding the major Type-IV pilus monomer found in many bacterial species. The system contains at least four signaling proteins: a SK with a protoglobin sensor domain (NmpU), a hybrid SK (NmpS), a phospho-sink protein (NmpT), and an NtrC-like RR (NmpR). We demonstrate that ΔpilR bypass suppressor mutations affect regulation of the NmpRSTU multi-component system, such that NmpR activation is capable of restoring expression of pilA in the absence of PilR. Our findings indicate that pilus gene expression in M. xanthus is regulated by an extended network of TCS which interact to refine control of pilus function.

The role of red coloration and song in peacock spider courtship: insights into complex signaling systems

Author(s): Girard, MB; Kasumovic, MM; Elias, DO | Abstract: Research on animal signaling enhances our understanding of links between sensory processing, decision making, behavior, and evolution. Studies of sexually-selected signals may be particularly informative as mate choice provides access to decision patterns in the way that courtship leads to an easily observable behavioral output in choosers, i.e., mating. Male peacock spiders have some of the most elaborate and varied courtship displays known among animals. Particularly striking to human observers is the diversity of red, orange, and yellow ornaments that males exhibit across the genus. The primary objective of our research was to investigate how these visual ornaments interact with vibratory songs to affect female mating behavior of one species, Maratus volans. Accordingly, we conducted mating trials under a series of experimentally manipulated vibratory and lighting conditions. Contrary to expectation, chromatic characteristics of longer wavelength ornaments are not driving female mate choice decisions, despite their extensive presence on male fans. Instead, our results suggest that contrast is important to females. Additionally, we found that vibratory signals were not necessary and did not increase mating rates. Our study demonstrates the intricacies inherent in complex signaling systems.

Evidence for changing nerve growth factor signalling mechanisms during development, maturation and ageing in the rat molar pulp

To examine rat molar pulp innervation and identify complex cellular signalling systems involving nerve growth factor (NGF) and its p75 receptors (NGFR) at different stages of development, maturation and ageing. Decalcified mandibular first molar mesial cusps from Wistar rats of ages 0day; 1, 2, 3, 4, 6, 9, 12 and 24weeks (n=5 per group) were sectioned (10μm) and incubated with antibodies for NGF, NGFR, calcitonin gene-related peptide (CGRP) and neurofilament. Nerve densities in worn and intact regions of 3- to 24-week-old rats were compared by anova, Bonferroni and t-tests. During odontogenesis, differences in NGF and NGFR expression were observed, with no evidence of nerve fibres, suggesting a signalling mechanism controlling cellular differentiation and dentine formation. Tooth wear in 4-week rats was associated with reduced NGF expression and significantly decreased CGRP axons within affected odontoblast regions. The underlying subodontoblasts started expressing NGF which continued until 9weeks. This may promote a significant increase in CGRP nerve density in affected regions. Nerve density in intact odontoblast regions increased gradually and reached significant levels in 12-week rats. Reduction in nerve densities within worn and intact regions of cusps was observed at 24weeks. Age-related changes and responses to tooth wear may be controlled by the NGF signalling mechanism, with roles in odontoblast/subodontoblast communication and control of sensory innervation at different stages of tooth development, maturation and ageing. Greater understanding of cellular and nerve regulation in the injured pulp may promote therapeutic strategies for pulp survival.

Alternative Splicing and Cross-Talk with Light Signaling.

Alternative splicing (AS) is the main source of proteome diversity that in large part contributes to the complexity of eukaryotes. Recent global analysis of AS with RNA sequencing has revealed that AS is prevalent in plants, particularly when responding to environmental changes. Light is one of the most important environmental factors for plant growth and development. To optimize light absorption, plants evolve complex photoreceptors and signaling systems to regulate gene expression and biological processes in the cell. Genome-wide analyses have shown that light induces intensive AS in plants. However, the biochemical mechanisms of light regulating AS remain poorly understood. In this review, we aim to discuss recent progress in investigating the functions of AS, discovery of cross-talk between AS and light signaling, and the potential mechanism of light-regulated AS. Understanding how light signaling regulates the efficiency of AS and the biological significance of light-regulated AS in plant systems will provide new insights into the adaptation of plants to their environment and, ultimately, crop improvement.

Environmental adaptation of Acanthamoeba castellanii and Entamoeba histolytica at genome level as seen by comparative genomic analysis.

Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. Acanthamoeba castellanii is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; Entamoeba histolytica is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of A. castellanii. Nevertheless, both species prosper, demonstrating fitness to their specific environments. Here we compare transcriptomes of A. castellanii and E. histolytica with application of orthologs' search and gene ontology to learn how different life strategies influence genome evolution and restructuring of physiology. A. castellanii demonstrates great metabolic activity and plasticity, while E. histolytica reveals several interesting features in its translational machinery, cytoskeleton, antioxidant protection, and nutritional behavior. In addition, we suggest new features in E. histolytica physiology that may explain its successful colonization of human colon and may facilitate medical research.

Deregulated TGF-β/BMP Signaling in Vascular Malformations.

Correct organization of the vascular tree requires the balanced activities of several signaling pathways that regulate tubulogenesis and vascular branching, elongation, and pruning. When this balance is lost, the vessels can be malformed and fragile, and they can lose arteriovenous differentiation. In this review, we concentrate on the transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) pathway, which is one of the most important and complex signaling systems in vascular development. Inactivation of these pathways can lead to altered vascular organization in the embryo. In addition, many vascular malformations are related to deregulation of TGF-β/BMP signaling. Here, we focus on two of the most studied vascular malformations that are induced by deregulation of TGF-β/BMP signaling: hereditary hemorrhagic telangiectasia (HHT) and cerebral cavernous malformation (CCM). The first of these is related to loss-of-function mutation of the TGF-β/BMP receptor complex and the second to increased signaling sensitivity to TGF-β/BMP. In this review, we discuss the potential therapeutic targets against these vascular malformations identified so far, as well as their basis in general mechanisms of vascular development and stability.

Measuring inotocin receptor gene expression in chronological order in ant queens

In vertebrates and invertebrates, oxytocin/vasopressin-like peptides modulate a variety of behaviors. The recent discovery of the gene and receptor sequences of inotocin, the insect ortholog of oxytocin/vasopressin, opens new opportunities for understanding the role of this peptide family in regulating behaviors in the most populated class of living animals. Ants live in highly organized colonies. Once a year, they produce future queens that soon leave the nest to mate and found new colonies. During the first months of their lives, ant queens display a sequence of behaviors ranging from copulation and social interactions to violent fighting. In order to investigate the potential roles of inotocin in shaping queen behavior, we measured gene expression of the inotocin receptor in the heads of Lasius niger ant queens at different points in time. The highest levels of expression occurred early in queen life when they experience crowded conditions in their mother nests and soon thereafter set out to mate. Inotocin could thus be involved in regulating social and reproductive behaviors as reported in other animals. While oxytocin and vasopressin are also involved in aggression in mammals, we found no direct link between these behaviors and inotocin receptor expression in L. niger. Our study provides a first glimpse into the roles the inotocin receptor might play in regulating important processes in ant physiology and behavior. Further studies are needed to understand the molecular function of this complex signaling system in more detail.

Deciphering the Complex Signaling Systems That Regulate Intestinal Epithelial Cell Death Processes and Shedding.

Intestinal epithelial cells play a fundamental role in maintaining homeostasis. Shedding of intestinal cells in a controlled manner is critical to maintenance of barrier function. Barrier function is maintained during this shedding process by a redistribution of tight junctional proteins to facilitate closure of the gap left by the shedding cell. However, despite the obvious importance of epithelial cell shedding to gut health, a central question is how the extrusion of epithelial cells is achieved, enabling barrier integrity to be maintained in the healthy gut and restored during inflammation remains largely unanswered. Recent studies have provided evidence that excessive epithelial cell shedding and loss of epithelial barrier integrity is triggered by exposure to lipopolysaccharide or tumor necrosis factor alpha. Subsequent studies have provided evidence of the involvement of specific cellular components and signaling mechanisms as well as the functionality of microbiota that can be either detrimental or beneficial for intestinal barrier integrity. This review will focus on the evidence and decipher how the signaling systems through which the mucosal immune system and microbiota can regulate epithelial cell shedding and how these mechanisms interact to preserve the viability of the epithelium.

Organ-Specific Differences in Endothelial Permeability-Regulating Molecular Responses in Mouse and Human Sepsis.

ABSTRACTIn patients with sepsis-induced multi-organ dysfunction syndrome, diverging patterns of oedema formation and loss of function in organs such as lung and kidney suggest that endothelial permeability-regulating molecular responses are differentially regulated. This potential differential regulation has been insufficiently studied at the level of components of adherens and tight junctions. We hypothesized that such a regulation by endothelial cells in sepsis takes place in an organ-specific manner. We addressed our hypothesis by studying by quantitative real time polymerase chain reaction the expression of a predefined subset of EC permeability-related molecules (occludin, claudin-5, PV-1, CD-31, endomucin, Angiopoietin-1, Angiopoietin-2, Tie2, VEGFA, VEGFR1, VEGFR2, and VE-cadherin) in kidney and lung after systemic lipopolysacharide injection in mice, and in kidneys of patients who died of sepsis. We showed that baseline endothelial expression of permeability-related molecules differs in mouse kidney and lung. Moreover, we showed differential regulation of these molecules after lipopolysacharide injection in the two mouse organs. In lung we found a decrease in expression levels of molecules of the adherence and tight junctions complex and related signaling systems, compatible with increased permeability. In contrast, in kidney we found expression patterns of these molecules compatible with decreased permeability. Finally, we partially corroborated our findings in mouse kidney in human kidneys from septic patients. These findings may help to understand the clinical difference in the extent of oedema formation in kidney and lung in sepsis-associated organ failure.

Vocal plasticity in a reptile.

Sophisticated vocal communication systems of birds and mammals, including human speech, are characterized by a high degree of plasticity in which signals are individually adjusted in response to changes in the environment. Here, we present, to our knowledge, the first evidence for vocal plasticity in a reptile. Like birds and mammals, tokay geckos (Gekko gecko) increased the duration of brief call notes in the presence of broadcast noise compared to quiet conditions, a behaviour that facilitates signal detection by receivers. By contrast, they did not adjust the amplitudes of their call syllables in noise (the Lombard effect), which is in line with the hypothesis that the Lombard effect has evolved independently in birds and mammals. However, the geckos used a different strategy to increase signal-to-noise ratios: instead of increasing the amplitude of a given call type when exposed to noise, the subjects produced more high-amplitude syllable types from their repertoire. Our findings demonstrate that reptile vocalizations are much more flexible than previously thought, including elaborate vocal plasticity that is also important for the complex signalling systems of birds and mammals. We suggest that signal detection constraints are one of the major forces driving the evolution of animal communication systems across different taxa.

SiGNet: A signaling network data simulator to enable signaling network inference.

Network models are widely used to describe complex signaling systems. Cellular wiring varies in different cellular contexts and numerous inference techniques have been developed to infer the structure of a network from experimental data of the network’s behavior. To objectively identify which inference strategy is best suited to a specific network, a gold standard network and dataset are required. However, suitable datasets for benchmarking are difficult to find. Numerous tools exist that can simulate data for transcriptional networks, but these are of limited use for the study of signaling networks. Here, we describe SiGNet (Signal Generator for Networks): a Cytoscape app that simulates experimental data for a signaling network of known structure. SiGNet has been developed and tested against published experimental data, incorporating information on network architecture, and the directionality and strength of interactions to create biological data in silico. SiGNet is the first tool to simulate biological signaling data, enabling an accurate and systematic assessment of inference strategies. SiGNet can also be used to produce preliminary models of key biological pathways following perturbation.

Molecular and Cellular Mechanisms of AtrialFibrosis in AtrialFibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Atrial fibrosis has emerged as an important pathophysiological contributor and has been linked to AF recurrences, resistance to therapy and complications. Here, the author reviews the molecular and cellular mechanisms that control atrial fibrosis. It is important to note that not all tissue fibrosis is identical. For example, reactive (interstitial) fibrosis increases the amount of collagen between cardiac muscle bundles without fundamentally altering muscle bundle architecture. Replacement (reparative) fibrosis replaces dead cardiomyocytes with extracellular matrix tissue and fibroblasts, preserving tissue integrity at the expense of muscle bundle continuity. Replacement fibrosis may be much more disruptive to electric conduction and more difficult to reverse than reactive fibrosis. The author reviews the complex signaling systems that cause fibrosis, including those connected to connective tissue growth factor, angiotensin-II, platelet-derived growth factor, and transforming growth factor-β. The author then considers the molecular constitution of fibrous tissue, including the production and maturation of collagen and the roles of important extracellular matrix proteins such as fibronectin, tenascin-C, and thrombospodin-1. The author then discusses the evolving evidence for an important role of Ca2+ entry in the profibrotic activation of fibroblasts, along with evidence that dysregulation of Ca2+-transporting transient potential receptor channels and inward rectifier K+ channels in AF fibroblasts is profibrotic. Finally, the author reviews the evidence for micro-ribonucleic acid involvement in atrial fibrotic signaling and AF promotion. It is hoped that an improved understanding of the mechanisms controlling atrial fibrosis will open up new opportunities for AF prevention and management.

Uterine Fibroids Review: Understanding their Origins to Better Understand their Future Treatments

Despite the high prevalence and the enormous impact the uterine fibroids has on the healthcare system and the economy, there is no effective medical treatment available to eliminate fibroids. This is due in part to the fact that very little is known about their pathophysiology; in order to look for and potentially find treatments capable of eliminating fibroids, we must gain a deep understanding of the mechanisms behind their initiation, stimulation, and growth. In this article, we comprehensively review current knowledge of the pathogenesis of uterine fibroids, with the aim of better understanding their origin, as well as discussing the action of already existing medical treatments in order to highlight ways that potential future therapies may be able to target the disease. A literature search was performed in PubMed to find articles related to the etiopathogenesis of fibroids and their treatments. Myomas comprise areas of disordered smooth muscle fascicles characterized by an excess of acellular extracellular matrix (ECM) with a dysregulated phenotype. Although the initial event is believed to be smooth muscle cell proliferation, it is thought that a complex signaling system is also necessary. Non-hormonal factors may be responsible for initiating the development of uterine fibroids, although hormonal stimulation is an essential factor for their growth Recent studies have confirmed that the different cell types contained in fibroids are all clonally derived from a parental cell with implied multipotent stem cell properties. Ethnicity also strongly influences the development and clinical severity of fibroids. Many Growth factors and their respective receptors have been implicated in fibroid growth. The available evidence continues to reinforce the importance of progesterone in the development of fibroids. The Ulipristal Acetate mediated volume reduction is due to a series of multifactorial and successive events that lead to a low proliferation rate.

The other genome: Pathways for the Effects of the Microbiome on Metabolism, Behavior, and mental Disorders

Overall Abstract Major efforts are ongoing to unravel the genomic basis of psychiatric disorders, with a focus on the human genome. The amount of microbial cells exceeds that of human cells in our bodies. The immense amount of non-human DNA within our bodies is not captured by traditional human genomic studies. Our microbial component is represented by approximately 1,000 different species. This symposium will address the behavioral effects of our “other genome”: the human microbiome. The microbiota–gut–brain (MGB) axis is a complex multiorgan bidirectional signaling system between the microbiota and the brain that plays a fundamental role in host physiology, homeostasis, development, metabolism and behavior. Growing evidence shows reproducible and consistent effects of microbial states on behavior, supporting a role for the microbiota in modulating behavior. Differences in anxiety-related behaviors are commonly reported in mice with altered gut microbiomes, implicating the role of gut microbiota in stress and depression. In this symposium, Dr. Omry Koren, Bar-Ilan University, Israel, will present data on how microbes can influence mood and behavior. Dr. Peng Xie, Chongqing Medical University, China, will present exciting new data showing that the absence of gut microbiota in germ-free mice results in decreased depressive-like behavior. His team shows that from clinical sampling, the gut microbiotic compositions of healthy controls are significantly different from those of depressed patients. Finally, fecal microbiota transplantation of germ-free mice with ‘depression microbiota’ from depressed patients results in depression-like behaviors compared with colonization with ‘healthy microbiota’ from healthy individuals. Moreover, they showed that mice harboring ‘depression microbiota’ primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism, indicating that the development of depressive-like behaviors is mediated through the host’s metabolism. Dr. Julio Licinio, South Australian Health & Medical Research Institute (SAHMRI) and Flinders University, Australia, will show data on how a model of chronic stress, resulting in depressive-like behaviors, causes change in gut microbiota composition. Dr. Ma-Li Wong, SAHMRI and Flinders, Australia, will present data demonstrating that that the inflammasome, as evidenced by genetic or pharmacologic inhibition of caspase 1, mediates behavioral changes that might be brought about through the MGB axis. In this symposium we will demonstrate that MGB axis is fully bidirectional, functioning in a manner through which variation in microbiota affect behavior, while alterations in behavior, brought about by chronic stress, genetic manipulation or pharmacological intervention, result in changes in the gut microbiota. Further elucidation of the MGB axis may offer novel therapeutic targets for psychiatric disorders.

Inflammasome Signalling Modulate The Effects Of The Microbiome On Behavior

The microbiota-gut-brain (MGB) axis is a complex multi-organ bidirectional signaling system between the microbiota and the brain that plays a fundamental role in host physiology, homeostasis, development and metabolism. We tested whether antagonism of caspase-1 (casp1) would result in gut microbiome changes. Pharmacological antagonism of inflammasome signaling using the casp1 antagonist minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Either chronic stress or pharmacological inhibition of casp1 altered the fecal microbiome in a very similar manner. Gut microbiota changes in stressed mice treated with minocycline included increased relative abundance of Akkermansia spp and Blautia spp, which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota respectively, and increment in Lachnospiracea abundance which was consistent with microbiota changes of casp1 deficiency. The protective effect of casp1 inhibition may involve modulation of the relationship between stress and gut microbiota composition, through which the gut microbiota via inflammasome signaling modulates pathways that will alter brain function, and affect depressive- and anxiety-like behaviors.

Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment.

It has long been known that the tumor microenvironment contributes to the proliferation and survival of neoplasms through the constant interaction with the stromal and immune compartments. In this investigation, we explored the role of cancer-associated fibroblasts (CAFs) in the regulation of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) though a complex intercellular BDNF-TrkB signaling system. Our studies show that conditioned media derived from patient-derived CAFs promoted HNSCC cell proliferation, in vitro cell migration, cell invasion and chemotherapy resistance, compared to normal fibroblasts. Furthermore, examination of the in vivo impact of CAF pathophysiology in the tumor microenvironment in animal xenograft models revealed that HNSCC cell lines in combination with CAFs promoted tumor growth and increased incidence of lymphovascular metastasis as compared to injection of tumor cells or CAF cells alone. Using pharmacological and genetic alterations, we mechanistically demonstrate the critical importance of BDNF-TrkB signaling in the tumor microenvironment. These investigations further support the rationale for BDNF/TRKB targeted therapy against in the treatment of HNSCC.

Role of Phosphorylated HDAC4 in Stroke-Induced Angiogenesis

Acetylation or deacetylation of chromatin proteins and transcription factors is part of a complex signaling system that is involved in the control of neurological disorders. Recent studies have demonstrated that histone deacetylases (HDACs) exert protective effects in attenuating neuronal injury after ischemic insults. Class IIa HDAC4 is highly expressed in the brain, and neuronal activity depends on the nucleocytoplasmic shuttling of HDAC4. However, little is known about HDAC4 and its roles in ischemic stroke. In this study, we report that phosphorylation of HDAC4 was remarkably upregulated after stroke and blockade of HDAC4 phosphorylation with GÖ6976 repressed stroke-induced angiogenesis. Phosphorylation of HDAC4 was also increased in endothelial cells hypoxia model and suppression of HDAC4 phosphorylation inhibited the tube formation and migration of endothelial cells in vitro. Furthermore, in addition to the inhibition of angiogenesis, blockade of HDAC4 phosphorylation suppressed the expression of genes downstream of HIF-VEGF signaling in vitro and in vivo. These data indicate that phosphorylated HDAC4 may serve as an important regulator in stroke-induced angiogenesis. The protective mechanism of phosphorylated HDAC4 is associated with HIF-VEGF signaling, implicating a novel therapeutic target in stroke.

Protective roles of hepatic GABA signaling in acute liver injury of rats.

γ-Aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes. The function of hepatic GABA signaling system in rats was examined using models of d-galactosamine (GalN)-induced acute hepatocytic injury in vivo and in vitro. The expression of GAD increased whereas GABAAR subunits decreased in the liver of GalN-treated rats. Remarkably, treating rats with GABA or the GABAAR agonist muscimol, but not the GABABR agonist baclofen, protected hepatocytes against GalN toxicity and improved liver function. In addition, muscimol treatment decreased the formation of pseudobile ductules and the enlargement of hepatocytic canaliculi in GalN-treated rats. Our results revealed that a complex GABA signaling system exists in the rat liver. Activation of this intrahepatic GABAergic system protected the liver against toxic injury.NEW & NOTEWORTHY Auto- and paracrine GABAergic signaling systems exist in the rat hepatocytes and cholangiocytes. Activation of GABA signaling protects liver function from d-galactosamine injury by reducing toxic impairment of hepatocytes and by decreasing cholangiocyte proliferation.

Humans attribute emotions to a robot that shows simple behavioural patterns borrowed from dog behaviour

In social robotics it has been a crucial issue to determine the minimal set of relevant behaviour actions that humans interpret as social competencies. As a potential alternative of mimicking human abilities, it has been proposed to use a non-human animal, the dog as a natural model for developing simple, non-linguistic emotional expressions for non-humanoid social robots. In the present study human participants were presented with short video sequences in which a PeopleBot robot and a dog displayed behaviours that corresponded to five emotional states (joy, fear, anger, sadness, and neutral) in a neutral environment. The actions of the robot were developed on the basis of dog expressive behaviours that had been described in previous studies of dog–human interactions. In their answers to open-ended questions, participants spontaneously attributed emotional states to both the robot and the dog. They could also successfully match all dog videos and all robot videos with the correct emotional state. We conclude that our bottom up approach (starting from a simpler animal signalling system, rather than decomposing complex human signalling systems) can be used as a promising model for developing believable and easily recognisable emotional displays for non-humanoid social robots.