Project description:The vomeronasal organ of mice consists of two major types of vomeronasal sensory neurons (VSNs) expressing either receptors of the V1R or V2R family. V1R and V2R VSNs form from a common pool of progenitors but have distinct differentiation programs. We analyzed single cell RNA sequencing data of adult VNO and identified differential expression of Notch1 receptor and Dll4 ligand among the neuronal precursors at the VSN dichotomy. We further demonstrated that Notch signaling is required for effective differentiation of V2R+ basal VSNs.
Project description:Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Traditionally, 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 structure of the rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons (VSNs). Here we demonstrated that the identity of postmitotic/maturing VSNs and vomeronasal dependent behaviors can be reprogrammed through the rescue of AP-2e expression in the AP-2eNull mice and by inducing ectopic AP-2e expression in mature apical VSNs. Our data suggest that the transcription factor AP-2e directly controls the expression of batteries of vomeronasal genes.
Project description:We have generated single cell transcriptomic atlases of vomeronasal organs (VNO) from juvenile and adult mice. Combined with spatial molecular imaging, we uncover a distinct, previously unidentified class of cells that express the vomeronasal receptors and a population of canonical olfactory sensory neurons in the VNO. High resolution trajectory and cluster analyses reveal the lineage relationship, spatial distribution of cell types, and a putative cascade of molecular events that specify the V1r, V2r, and OR lineages from a common stem cell population. The expression of vomeronasal and olfactory receptors follow power law distributions, but there are high variabilities in average expression levels between individual receptor and cell types. Substantial co-expression is found between receptors across clades, from different classes, and between olfactory and vomeronasal receptors, with nearly half from pairs located on the same chromosome. Interestingly, the expression of V2r, but not V1r, genes is associated with various transcription factors, suggesting distinct mechanisms of receptor choice associated with the two cell types. We identify association between transcription factors, surface axon guidance molecules, and individual VRs, thereby uncovering a molecular code that guides the specification of the vomeronasal circuitry. Our study provides a wealth of data on the development and organization of the accessory olfactory system at both cellular and molecular levels to enable a deeper understanding of vomeronasal system function.
Project description:<1. The vomeronasal organ (VNO) in the nose of most tetrapods is a sensory structure for the detection of pheromones and kairomones (intra-specific and inter-specific chemical signals) that initiate innate behaviours. It has two neuronal layers, each expressing distinct receptor sub-families coupled to different G-proteins. Neurones in the apical layer express a single vomeronasal receptor type 1 and the G?i2 G-protein. On the other hand, neurons in the basal layer express two or more vomeronasal receptors type-2 (V2Rs) and the G?o G-protein. In mice, V2Rs are organized into four families, A, B, D and C, with family-A and -C sub-divided into subfamilies A1-A10 and C1-C2. These gene families are expressed in a unique combinatorial pattern. Families A (subfamilies A1-A6), B and D are expressed monogenically and coexpress with the recently expanded family-C2 (6 genes, Vmn2r2 to Vmn2r7). While neurons expressing the phylogenetically ancient subfamily-C2 (1 gene, Vmn2r1) coexpress with family-BD and subfamilies A8-A10.We have generated a knock-out mouse for gene Vmn2r1 gene, using a Eucomm tm1b allele. This mouse is a valuable resource for further understanding the molecular organization of the VNO and its behavioural implications, in an evolutionary context. We propose here, to sequence the VNO of Vmn2r1 mutant mice. By studying the VNO transcriptome we hope to advance our knowledge of the genetic coding of pheromonal communication. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:We performed RNaseq of liver, hypothalamus and vomeronasal organ crosses between inbred stains of M. m. domesticus (strain WSB/EiJ) and M. m. musculus (PWD/PhJ). We also sequenced RNA from the same tissues from parental M. m. musculus (PWD/PhJ).
Project description:The Vomeronasal organ (VNO) is a part of the accessory olfactory system, which is responsible for detecting pheromones, chemical factors that trigger a spectrum of sexual and social behaviors. The vomeronasal epithelium (VNE) shares several features with the epithelium of the main olfactory epithelium (MOE). However, it is a distinct neuroepithelium populated by chemosensory neurons that differ from the olfactory sensory neurons (OSNs) in cellular structure, receptor expression, and connectivity. The vomeronasal organ of rodents comprises a sensory epithelium and a thin nonsensory epithelium that morphologically resembles the respiratory epithelium. Sox2-positive cells have been previously identified as the stem cell population that gives rise to neuronal progenitors in MOE and VNE. In addition to these, the MOE also comprises p63 positive horizontal basal cells (HBCs), a second pool of quiescent stem cells that become active in response to injury. Immunolabeling against the transcription factor p63, Keratin-5 (Krt5), Krt14 and Krt5Cre tracing experiments highlighted the existence of horizontal basal cells distributed along the basal lamina of the VNO forming from progenitors along the basal lamina oft the marginal zones. Moreover, these experiments revealed that the NSE of rodents is, like the respiratory epithelium, a stratified epithelium where the p63/Krt5+ basal cells self-replicate and give rise to the apical columnar cells facing the lumen of the VNO.
Project description:The vomeronasal organ (VNO) of mice contains two main types of vomeronasal sensory neurons (VSNs)- Apical and Basal. Apical VSNs express vomeronasal receptors (VRs) of the V1R family and project to the anterior accessory olfactory bulb (AOB) and VSNs in the basal portions of the epithelium express receptors of the V2R family and project to the posterior portion of the AOB. In the vomeronasal epithelium of mice we found active BMP signaling. By generating Smad4 conditional mutants we disrupted canonical TGF-b/BMP signaling in either maturing basal VSNs or in mature apical and basal VSNs.