Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP-2ε in vomeronasal sensory neurons

Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remains a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here we demonstrated that the identity of postmitotic/maturing VSNs and vomeronasal dependent behaviors can be reprogrammed through the rescue of AP-2ε expression in the AP-2ε Null mice and by inducing ectopic AP-2ε expression in mature apical VSNs. We suggest that the transcription factor AP-2ε can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes.

Histological Features of the Nasal Passage in Juvenile Japanese White Rabbits

Rabbits are sometimes used for intranasal toxicology studies. We investigated the postnatal development of the nasal passage in juvenile Japanese white rabbits from just after birth to 6-week-old to provide information for conducting intranasal toxicological evaluation using juvenile animals. On postnatal day (PND) 1, the nasal passage consisted of the septum with mostly cartilaginous nasal wall and turbinates. The lining squamous, transitional, respiratory, and olfactory epithelia were already distributed similar to adults and were still underdeveloped. The nasal passage gradually expanded with age, as did the nasal wall, including the turbinates formed by endochondral ossification. The maxilloturbinate elongated, during which it branched complexly. The respiratory epithelium takes the form of columnar epithelium together with a reduction in goblet cells. In addition, the olfactory epithelium had clear cytoplasm in the ethmoturbinate, the olfactory nerve bundles thickened, and Bowman’s gland acini increased in size and number. Other tissues, including the vomeronasal organ, nasal-associated lymphoid tissue, and nasolacrimal duct, also developed histologically with age. This investigation characterized the postnatal histological development of the nasal passage in Japanese white rabbits, providing basic knowledge regarding the histological examination and rationale for appropriate study design of intranasal toxicology studies in juvenile rabbits.

Does a third intermediate model for the vomeronasal processing of information exist? Insights from the macropodid neuroanatomy

The study of the α-subunit of Gi2 and Go proteins in the accessory olfactory bulb (AOB) was crucial for the identification of the two main families of vomeronasal receptors, V1R and V2R. Both families are expressed in the rodent and lagomorph AOBs, according to a segregated model characterized by topographical anteroposterior zonation. Many mammal species have suffered from the deterioration of the Gαo pathway and are categorized as belonging to the uniform model. This scenario has been complicated by characterization of the AOB in the tammar wallaby, Notamacropus eugenii, which appears to follow a third model of vomeronasal organization featuring exclusive Gαo protein expression, referred to as the intermediate model, which has not yet been replicated in any other species. Our morphofunctional study of the vomeronasal system (VNS) in Bennett’s wallaby, Notamacropus rufogriseus, provides further information regarding this third model of vomeronasal transduction. A comprehensive histological, lectin, and immunohistochemical study of the Bennett’s wallaby VNS was performed. Anti-Gαo and anti-Gαi2 antibodies were particularly useful because they labeled the transduction cascade of V2R and V1R receptors, respectively. Both G proteins showed canonical immunohistochemical labeling in the vomeronasal organ and the AOB, consistent with the anterior–posterior zonation of the segregated model. The lectin Ulex europaeus agglutinin selectively labeled the anterior AOB, providing additional evidence for the segregation of vomeronasal information in the wallaby. Overall, the VNS of the Bennett’s wallaby shows a degree of differentiation and histochemical and neurochemical diversity comparable to species with greater VNS development. The existence of the third intermediate type in vomeronasal information processing reported in Notamacropus eugenii is not supported by our lectin-histochemical and immunohistochemical findings in Notamacropus rufogriseus.

Spatiotemporal Protein Expression Profiles of QSOX1 in the Murine Uterus, Placenta, and Embryo during Pregnancy

Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) catalyzes the oxidation of the sulfhydryl group to disulfide bond and is widely expressed in various tissues. This study focuses on investigating QSOX1′s spatiotemporal and cellular protein expression profile of the pregnant uterus, placenta, and developing embryo during mouse pregnancy. Immunohistochemical staining was used to reveal the localization of QSOX1 protein, and HistoQuest was applied to quantify protein levels. The expression level of QSOX1 in the decidua and muscle cells of the pregnant uterus fluctuated dramatically during pregnancy. QSOX1 was ubiquitously expressed in the labyrinth, junction zone, and chorionic plate in the placenta. The quantitative analysis found that this protein was highly expressed in the spinal cord, lens, midbrain, cerebellum, medulla oblongata, and tooth of mouse embryos, followed by the heart, intercostal muscle, diaphragm, intermediate zone, extrinsic ocular muscle, spine, pons, epidermis, tongue, ganglion, vomeronasal organ, thoracic vertebrae, and thymus. Interestingly, QSOX1 was also markedly expressed in olfactory system tissues. This comprehensive spatiotemporal study of QSOX1 protein expression will provide a basis for further investigations of the QSOX1 physiological function in the pregnant uterus, placenta, and developing embryo.

Does a Third Model for the Vomeronasal Processing of Information Exist? Insights from the Macropodid Neuroanatomy

The study of the α-subunit of Gi2 and Go proteins in the accessory olfactory bulb (AOB) was crucial for the identification of the two main families of vomeronasal receptors, V1R and V2R. Both families are expressed in the rodent and lagomorph AOBs, according to a segregated model characterized by topographical anteroposterior zonation. Many mammal species have suffered from the deterioration of the Gαo pathway and are categorized as belonging to the uniform model. This scenario has been complicated by characterization of the AOB in the tammar wallaby, Macropus eugenii, which appears to follow a third model of vomeronasal organization featuring exclusive Gαo protein expression, referred to as the intermediate model, which has not yet been replicated in any other species. Our morphofunctional study of the vomeronasal system (VNS) in Bennett’s wallaby, Macropus rufogriseus, provides further information regarding this third model of vomeronasal transduction.A comprehensive histological, lectin, and immunohistochemical study of the Bennett’s wallaby VNS was performed. Anti-Gαo and anti-Gαi2 antibodies were particularly useful because they labeled the transduction cascade of V2R and V1R receptors, respectively. Both G proteins showed canonical immunohistochemical labeling in the vomeronasal organ and the AOB, consistent with the anterior-posterior zonation of the segregated model. The lectin Ulex europaeus agglutinin selectively labeled the anterior AOB, providing additional evidence for the segregation of vomeronasal information in the wallaby.Overall, the VNS of the Bennett’s wallaby shows a degree of differentiation and histochemical and neurochemical diversity comparable to species with greater VNS development, which does not support the existence of a third “intermediate” type of vomeronasal information processing.

The Microvillar and Solitary Chemosensory Cells as the Novel Targets of Infection of SARS-CoV-2 in Syrian Golden Hamsters

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.

Morphological and Histological Features of the Vomeronasal Organ in African Pygmy Hedgehog (Atelerix albiventris)

The vomeronasal organ (VNO) detects specific chemicals such as pheromones and kairomones. Hedgehogs (Eulipotyphla: Erinaceidae) have a well-developed accessory olfactory bulb that receives projections from the VNO, but little is known about the hedgehog VNO. Here, we studied the histological features of the VNO in five individual African pygmy hedgehogs by hematoxylin-eosin, periodic acid-Schiff, and Alcian blue stains. The hedgehog VNO comprises a hyaline cartilage capsule, soft tissue and epithelial lumen, and it branches from the site just before the incisive duct opening into the nasal cavity. The soft tissues contain several small mucous (or mucoserous) glands and a large serous gland, and many venous sinuses all around the lumen. The VNO lumen is round to oval throughout the hedgehog VNO, and the sensory epithelium lines almost the entire rostral part and medial wall of the middle part. These findings indicate that the VNO is functional and plays an important role in the hedgehog. Notably, the VNO apparently has a characteristic flushing mechanism with serous secretions like those of gustatory glands, which the hedgehog might frequently use to recognize the external environment.