The fly pharyngeal sense organs lie at the transition between external and internal nutrient-sensing mechanisms. Here we investigate the function of pharyngeal sweet gustatory receptor neurons, demonstrating that they express a subset of the nine previously identified sweet receptors and respond to stimulation with a panel of sweet compounds. We show that pox-neuro (poxn) mutants lacking taste function in the legs and labial palps have intact pharyngeal sweet taste, which is both necessary and sufficient to drive preferred consumption of sweet compounds by prolonging ingestion. Moreover, flies putatively lacking all sweet taste show little preference for nutritive or non-nutritive sugars in a short-term feeding assay. Together, our data demonstrate that pharyngeal sense organs play an important role in directing sustained consumption of sweet compounds, and suggest that post-ingestive sugar sensing does not effectively drive food choice in a simple short-term feeding paradigm.

Sabellarids, also known as honeycomb or sandcastle worms, when building their tubes, produce chemical signals (free fatty acids) that are responsible for larval settlement and the formation of three-dimensional aggregations. The larval palps and the dorsal hump (becoming the median organ in adults) are presumed to participate in such a substrate selection during settlement. Notably, the sabellariid median organ is an apparently unique organ among annelids that has been attributed with a sensory function and perhaps with some affinities to the nuchal organs of other polychaetes. Nevertheless, detailed investigations of this prominent character complex including ultrastructural examinations are lacking so far.

The present study is a cladistic analysis of morphological characters focusing on the file of the mandible, the apices of the maxillae, the rupturing device on the maxillae, the internal structures of the mouthparts, and the external morphology of the labial segments as well as the distribution of labial sensilla in true water bugs (Hemiptera: Heteroptera, infraorder Nepomorpha). The study is based on data referring to sixty-two species representing all nepomorphan families (Heteroptera), together with one outgroup species representing the infraorders Gerromorpha (Mesoveliidae). The morphological data matrix consists of forty-eight characters. The present hypothesis supports the monophyly of the Nepomorpha and the monophyly of all families. The new modification in the systematic classification has been proposed: ((Nepidae + Belostomatidae), (Diaprepocoridae + Corixidae + Micronectidae), (Ochteridae + Gelastocoridae), Aphelocheiridae, Potamocoridae, Naucoridae, Notonectidae, and (Pleidae + Helotrephidae)).

miR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. Both microRNAs are expressed in the bristle progenitors, and despite a difference in their seed sequence, they share this key common target. In miR-263a and miR-263b deletion mutants, loss of bristles appears to be sporadic, suggesting that the role of the microRNAs may be to ensure robustness of the patterning process by promoting survival of these functionally specified cells. In the context of the retina, this mechanism ensures that the interommatidial bristles are protected during the developmentally programmed wave of cell death that prunes excess cells in order to refine the pattern of the pupal retina.

Dopaminergic neurons of the descending diencephalospinal system are located in the posterior tuberculum (PT) in zebrafish (Danio rerio), and correspond in mammals to the A11 group in hypothalamus and thalamus. In the larval zebrafish, they are likely the only source of central dopaminergic projections to the periphery. Here, we characterized posterior tubercular dopaminergic fibers projecting to peripheral sense organs, with a focus on the lateral line neuromasts. We labeled and identified catecholaminergic neurons and their projections by combining two immunofluorescence techniques, (i) using an antibody against Tyrosine hydroxylase, and (ii) using an antibody against GFP in transgenic zebrafish expressing in catecholaminergic neurons either membrane-anchored GFP to track fibers, or a Synaptophysin-GFP fusion to visualize putative synapses. We applied the CLARITY method to 6 days old whole zebrafish larvae to stain and analyze dopaminergic projections by confocal microscopy. We found that all lateral line neuromasts receive direct innervation by posterior tubercular dopaminergic neurons, and tracked these projections in detail. In addition, we found dopaminergic fibers projecting to the anterior and posterior lateral line ganglia, and extensive central dopaminergic arborizations around the terminal projection field of the lateral line afferent neurons in the hindbrain medial octavolateralis nucleus (MON). Therefore, dopaminergic innervation may affect lateral line sense information at different processing stages. Additional dopaminergic fibers innervate the trigeminal ganglion, and we observed fine catecholaminergic fibers in the skin with arborization patterns similar to free sensory nerve endings. We also detected potentially dopaminergic fibers innervating inner ear sensory epithelia. Therefore, the diencephalospinal A11-type dopaminergic system may broadly modulate peripheral senses. We also briefly report peripheral sympathetic catecholaminergic projections labeled in our experiments, and their innervation of the developing intestine, swim bladder and abdominal organs.

Arthropods have numerous sense organs, which are adapted to their habitat. While some sense organs are similar in structure and function in all arthropod groups, structural differences in functionally related sense organs have been described, as well as the absence of particular sense organ subtypes in individual arthropod groups. Here we address the question of how the diverse structures of arthropod sense organs have evolved by analysing the underlying molecular developmental processes in a crustacean, an arthropod group that has been neglected so far. We have investigated the development of four types of chemo- and mechanosensory sense organs in the branchiopod Daphnia magna (Cladocera) that either cannot be found in arthropods other than crustaceans or represent adaptations to an aquatic environment. The formation of the sensory organ precursors shows greater similarity to the arthropod taxa Chelicerata and Myriapoda than to the more closely related insects. All analysed sense organ types co-express the proneural genes ASH and atonal regardless of their structure and function. In contrast, in Drosophila melanogaster, ASH and atonal expression does not overlap and the genes confer different sense organ subtype identities. We performed experimental co-expression studies in D. melanogaster and found that the combinatorial expression of ato and ASH can change the external structure of sense organs. Our results indicate a central role for ASH and Atonal family members in the emergence of structural variations in arthropod sense organs.

Copepoda is one of the crustacean taxa with still unresolved phylogenetic relationships within Tetraconata. Recent phylogenomic studies place them close to Malacostraca and Cirripedia. Little is known about the morphological details of the copepod nervous system, and the available data are sometimes contradictory. We investigated several representatives of the subgroup Calanoida using immunohistochemical labeling against alpha-tubulin and various neuroactive substances, combining this with confocal laser scanning analysis and 3D reconstruction. Our results show that the studied copepods exhibit only a single anterior protocerebral neuropil which is connected to the nerves of two protocerebral sense organs: the frontal filament organ and a photoreceptor known as the Gicklhorn's organ. We suggest, on the basis of its position and the innervation it provides, that Gicklhorn's organ is homologous to the compound eye in arthropods. With regard to the frontal filament organ, we reveal detailed innervation to the lateral protocerebrum and the appearance of spherical bodies that stain intensely against alpha tubulin. A potential homology of these bodies to the onion bodies in malacostacan crustaceans and in Mystacocarida is suggested. The nauplius eye in all the examined calanoids shows the same basic pattern of innervation with the middle cup sending its neurites into the median nerve, while the axons of the lateral cups proceed into both the median and the lateral nerves. The early development of the axonal scaffold of the nauplius eye neuropil from the proximal parts of the nauplius eye nerves follows the same pattern as in other crustaceans. In our view, this specific innervation pattern is a further feature supporting the homology of the nauplius eye in crustaceans.

Shaping of developing organs requires dynamic regulation of force and resistance to achieve precise outcomes, but how organs monitor tissue mechanical properties is poorly understood. We show that in developing Drosophila follicles (egg chambers), a single pair of cells performs such monitoring to drive organ shaping. These anterior polar cells secrete a matrix metalloproteinase (MMP) that specifies the appropriate degree of tissue elongation, rather than hyper- or hypo-elongated organs. MMP production is negatively regulated by basement membrane (BM) mechanical properties, which are sensed through focal adhesion signaling and autonomous contractile activity; MMP then reciprocally regulates BM remodeling, particularly at the anterior region. Changing BM properties at remote locations alone is sufficient to induce a remodeling response in polar cells. We propose that this small group of cells senses both local and distant stiffness cues to produce factors that pattern the organ's BM mechanics, ensuring proper tissue shape and reproductive success.

Somatic sexual dimorphisms outside of the nervous system in Drosophila melanogaster are largely controlled by the male- and female-specific Doublesex transcription factors (DSX(M) and DSX(F), respectively). The DSX proteins must act at the right times and places in development to regulate the diverse array of genes that sculpt male and female characteristics across a variety of tissues. To explore how cellular and developmental contexts integrate with doublesex (dsx) gene function, we focused on the sexually dimorphic number of gustatory sense organs (GSOs) in the foreleg. We show that DSX(M) and DSX(F) promote and repress GSO formation, respectively, and that their relative contribution to this dimorphism varies along the proximodistal axis of the foreleg. Our results suggest that the DSX proteins impact specification of the gustatory sensory organ precursors (SOPs). DSX(F) then acts later in the foreleg to regulate gustatory receptor neuron axon guidance. These results suggest that the foreleg provides a unique opportunity for examining the context-dependent functions of DSX.

Natural antisense transcripts (NATs) constitute a significant group of regulatory, long noncoding RNAs. They are prominently expressed in testis but are also detectable in other organs. NATs are transcribed at low levels and co-expressed with related protein coding sense transcripts. Nowadays NATs are generally considered as regulatory, long noncoding RNAs without closer focus on the inevitable interference between sense and antisense expression. This work describes a cellular system where sense and antisense transcription of a specific locus (SLC34A1/PFN3) is induced using epigenetic modifiers and CRISPR-Cas9. The renal cell lines HEK293 and HKC-8 do not express SLC34A1/PFN3 under normal culture conditions. Five-day exposure to dexamethasone significantly stimulates sense transcript (SLC34A1) levels and antisense (PFN3) minimally; the effect is only seen in HEK293 cells. Enhanced expression is paralleled by reduced sense promoter methylation and an increase in activating histone marks. Expression is further modulated by cassettes that stimulate the expression of sense or antisense transcript but disrupt protein coding potential. Constitutive expression of a 5'-truncated SLC34A1 transcript increases sense expression independent of dexamethasone induction but also stimulates antisense expression. Concordant expression is confirmed with the antisense knock-in that also enhances sense expression. The antisense effect acts on transcription in cis since transient transfection with sense or antisense constructs fails to stimulate the expression of the opposite transcript. These results suggest that bi-directional transcription of the SLC34A1/PFN3 locus has a stimulatory influence on the expression of the opposite transcript involving epigenetic changes of the promoters. In perspective of extensive, previous research into bi-directionally transcribed SLC34A loci, the findings underpin a hypothesis where NATs display different biological roles in soma and germ cells. Accordingly, we propose that in somatic cells, NATs act like lncRNAs-with the benefit of close proximity to a potential target gene. In germ cells, however, recent evidence suggests different biological roles for NATs that require RNA complementarity and double-stranded RNA formation.

Additive genetic variance (VA ) and total genetic variance (VG ) are core concepts in biomedical, evolutionary and production-biology genetics. What determines the large variation in reported VA /VG ratios from line-cross experiments is not well understood. Here we report how the VA /VG ratio, and thus the ratio between narrow and broad sense heritability (h(2) /H(2) ), varies as a function of the regulatory architecture underlying genotype-to-phenotype (GP) maps. We studied five dynamic models (of the cAMP pathway, the glycolysis, the circadian rhythms, the cell cycle, and heart cell dynamics). We assumed genetic variation to be reflected in model parameters and extracted phenotypes summarizing the system dynamics. Even when imposing purely linear genotype to parameter maps and no environmental variation, we observed quite low VA /VG ratios. In particular, systems with positive feedback and cyclic dynamics gave more non-monotone genotype-phenotype maps and much lower VA /VG ratios than those without. The results show that some regulatory architectures consistently maintain a transparent genotype-to-phenotype relationship, whereas other architectures generate more subtle patterns. Our approach can be used to elucidate these relationships across a whole range of biological systems in a systematic fashion.

The circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), median eminence (ME), and area postrema (AP), allow parenchyma cells to sense a variety of blood-derived substances and/or secreted peptides into blood circulation. In the present study, we examined continuous neurogenesis in the CVOs of adult mice. The immunohistochemistry of neural progenitor cell (NPC) marker proteins revealed that Math1- and Mash1-positive cells were observed in the discrete regions of CVOs, including the capillary plexus in the OVLT, the internal zone of the ME, and the lateral zone in the AP. A few Mash1- and Math1-positive cells were seen throughout the SFO, and many Math1- but not Mash1-positive cells were observed at the arcuate nucleus. Math-positive cells were often seen to localize in close proximity to the vasculature. Bromodeoxyuridine (BrdU) immunohistochemistry revealed the incorporation of BrdU in a subpopulation of Mash1-, Math1-, HuC/D-, and microtubule-associated protein 2 (MAP2)-positive cells. Mash1- and Math1-positive cells expressed exclusively high level of plasminogen, whereas a subpopulation of HuC/D- and MAP2-positive neurons expressed low or undetectable level of plasminogen. Thus, the present study demonstrates that newborn cells express NPC marker proteins and plasminogen to localize closely at vascular matrix and moreover differentiate into neurons expressing mature neuron marker proteins, indicating that new neurons are possibly generated to integrate into new neural circuits.

Although many long noncoding RNAs (lncRNAs) have been identified in human and other mammalian genomes, there has been limited systematic functional characterization of these elements. In particular, the contribution of lncRNAs to organ development remains largely unexplored. Here we analyse the expression patterns of lncRNAs across developmental time points in seven major organs, from early organogenesis to adulthood, in seven species (human, rhesus macaque, mouse, rat, rabbit, opossum and chicken). Our analyses identified approximately 15,000 to 35,000 candidate lncRNAs in each species, most of which show species specificity. We characterized the expression patterns of lncRNAs across developmental stages, and found many with dynamic expression patterns across time that show signatures of enrichment for functionality. During development, there is a transition from broadly expressed and conserved lncRNAs towards an increasing number of lineage- and organ-specific lncRNAs. Our study provides a resource of candidate lncRNAs and their patterns of expression and evolutionary conservation across mammalian organ development.

In this paper, I will provide a phenomenological analysis of somatic obsessions at times present in obsessive-compulsive disorder. I will compare two different types of bodily obsessions, which have a different neurological-physiological underpinning: anguishing awareness of one's own heartbeat and of one's own breathing. In addition, I will contrast these two with how one experiences one's own liver. I will use the concepts "tactility obsessions" and "motility obsessions", which I have coined for the purpose of this comparison. In other words, these are obsessions concerning the felt sense of one's autonomous organs and obsessions concerning one's ability to voluntarily move. Ultimately, I claim that the core lived experience in somatic obsessive-compulsive disorder should not only be understood as having to do with intruding and "distorted thoughts" concerning bodily processes, but could also be understood as having to do with a felt sense of our organs interrupting and intruding our daily lives.

Utricles are vestibular sense organs that encode linear head movements. They are composed of a sensory epithelium with type I and type II hair cells and supporting cells, sitting atop connective tissue, through which vestibular nerves project. We characterized utricular Cre expression in 11 murine CreER lines using the ROSA26tdTomato reporter line and tamoxifen induction at 6 weeks of age. This characterization included Calbindin2CreERT2, Fgfr3-iCreERT2, GFAP-A-CreER™, GFAP-B-CreER™, GLAST-CreERT2, Id2CreERT2, OtoferlinCreERT2, ParvalbuminCreERT2, Prox1CreERT2, Sox2CreERT2, and Sox9-CreERT2. OtoferlinCreERT2 mice had inducible Cre activity specific to hair cells. GLAST-CreERT2, Id2CreERT2, and Sox9-CreERT2 had inducible Cre activity specific to supporting cells. Sox2CreERT2 had inducible Cre activity in supporting cells and most type II hair cells. ParvalbuminCreERT2 mice had small numbers of labeled vestibular nerve afferents. Calbindin2CreERT2 mice had labeling of most type II hair cells and some type I hair cells and supporting cells. Only rare (or no) tdTomato-positive cells were detected in utricles of Fgfr3-iCreERT2, GFAP-A-CreER™, GFAP-B-CreER™, and Prox1CreERT2 mice. No Cre leakiness (tdTomato expression in the absence of tamoxifen) was observed in OtoferlinCreERT2 mice. A small degree of leakiness was seen in GLAST-CreERT2, Id2CreERT2, Sox2CreERT2, and Sox9-CreERT2 lines. Calbindin2CreERT2 mice had similar tdTomato expression with or without tamoxifen, indicating lack of inducible control under the conditions tested. In conclusion, 5 lines-GLAST-CreERT2, Id2CreERT2, OtoferlinCreERT2, Sox2CreERT2, and Sox9-CreERT2-showed cell-selective, inducible Cre activity with little leakiness, providing new genetic tools for researchers studying the vestibular periphery.

C. elegans uses specialized mechanoreceptor neurons to sense various mechanical cues. However, whether other tissues and organs in C. elegans are able to perceive mechanical forces is not clear. In this study, with a whole-cell patch-clamp recording, we show that body wall muscles (BWMs) in C. elegans convert mechanical energy into ionic currents in a cell-autonomous manner. Mechano-gated ion channels in BWMs are blocked in amiloride or cation-free solutions. A further characterization of physiological properties of mechano-gate ion channels in BMWs and a genetic screening show that mechanosensation in BMWs is not dependent on UNC-105 and well-defined mechano-gated ion channels MEC-4 and TRP-4 in C. elegans. Taken together, our results demonstrate that BWMs in C. elegans function as mechanoreceptors to sense mechanical stimuli with an amiloride-sensitive, non-selective cation channel.

Biotic and abiotic mechanical stimuli are ubiquitous in the environment, and are a widely used source of sensory information in arthropods. Spiders sense mechanical stimuli using hundreds of slit sense organs (small isolated slits, large isolated slits, groups of slits and lyriform organs) distributed across their bodies and appendages. These slit sense organs are embedded in the exoskeleton and detect cuticular strain. Therefore, the spatial pattern of these sensors can give clues into how mechanical stimuli from different sources might be processed and filtered as they are transmitted through the body. Here, we map the distribution of slit sense organs on the legs in two species of orb-weaving spider, A. diadematus and T. edulis, in which slit sense organ distribution has not previously been investigated. We image the spiders' legs using scanning electron microscopy, and trace the position and orientation of slits on these images to describe the distribution and external morphology of the slit sense organs. We show that both species have a similar distribution of slit sense organs, with small isolated slits occurring in consistent lines parallel to the long axis of the legs, whilst large isolated slits, groups of slits and lyriform organs appear in fixed positions near the leg joints. Our findings support what has been described in the literature for several other species of spider, which indicates that slit organ arrangement is conserved across spiders in different evolutionary lineages and with disparate hunting strategies. The dispersed distribution of small isolated slits along the whole length of the leg may be used to detect large-scale strain of the leg segment as a result of muscle activity or internal changes in haemolymph pressure.

Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

The ontogeny of lymphoid organs and the development of cells expressing immunoglobulin heavy chain (IgH) mRNA as well as cells containing immunoglobulin (IgM) were studied in Atlantic cod (Gadus morhua L.), a marine teleost. Head kidney and spleen appeared as the first lymphoid organs, present at the time of hatching, whereas thymus was observed in 9 mm larvae. Fully developed lymphoid organs were not achieved until after metamorphosis. Cells expressing IgH mRNA were detected in paraffin sections of larvae and juveniles by in situ hybridization. Positive cells were not detected in fish smaller than 33 mm (58 days after hatching). IgH mRNA expression coincided with the first appearance of immunoglobulin-positive cells as revealed by immunohistochemistry in the same animals.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread across the world and impacted global healthcare systems. For clinical patients, COVID-19 not only induces pulmonary lesions but also affects extrapulmonary organs. An ideal animal model that mimics COVID-19 in humans in terms of the induced systematic lesions is urgently needed. Here, we report that Syrian hamster is highly permissive to SARS-CoV-2 and exhibit diffuse alveolar damage and induced extrapulmonary multi-organs damage, including spleen, lymph nodes, different segments of alimentary tract, kidney, adrenal gland, ovary, vesicular gland and prostate damage, at 3-7 days post inoculation (dpi), based on qRT-PCR, in situ hybridization and immunohistochemistry detection. Notably, the adrenal gland is a novel target organ, with abundant viral RNA and antigen expression detected, accompanied by focal to diffuse inflammation. Additionally, viral RNA was also detected in the corpus luteum of the ovary, vesicular gland and prostate. Focal lesions in liver, gallbladder, myocardium, and lymph nodes were still present at 18 dpi, suggesting potential damage after disease. Our findings illustrate systemic histological observations and the viral RNA and antigen distribution in infected hamsters during disease and convalescence to recapitulate those observed in humans with COVID-19, providing helpful data to the pathophysiologic characterization of SARS-CoV-2-induced systemic disease and the development of effective treatment strategies.