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Single cell RNA sequencing of P10 and adult vomeronasal organ of OMPCreR26AP2e and Controls

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE192746 | GEO | 2022/06/06

REPOSITORIES: GEO

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Tfap2e/AP-2ε has both activating and repressive roles in controlling genetic programs of vomeronasal sensory neurons that underly sociosexual behavior in mice

Project description: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-2εNull 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.

2022-06-29 | GSE193139 | GEO

Differentially expressed genes in isolated postnatal AP2e WT and null VNOs

Project description:Understanding the molecular mechanisms defining and maintaining the identity of a specific neuronal cell type is a central goal in neuroscience. The vomeronasal organ (VNO) of mice contains hundreds of distinct vomeronasal sensory neurons (VSNs). The VSNs are classified into two major cell types that are segregated in apical and basal regions of the VNO, express vomeronasal receptors of different superfamilies, and send axons to different portions of the accessory olfactory bulb. How apical or basal identity of VSNs is established and maintained is largely unknown. Here we attempt to assess the role of a single transcription factor, AP-2ε, in the VNO of mice. We used microarrays to examine global effect of AP-2ε loss-of-function on gene expression in the vomeronasal organ.

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single cell RNA sequencing of adult (P60) vomeronasal organ

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Gene expression profiling from whole VNOs after tfap2eCre-mediated Smad4 ablation in immature basal vomeronasal neurons and OMPCre-mediated Smad4 ablation in all mature vomeronasal neurons

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.

2019-07-19 | GSE134492 | GEO

Single cell transcriptomics of vomeronasal neuroepithelium reveals a differential endoplasmic reticulum environment amongst neuronal subtypes

Project description:Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is thought to be mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ (VNO) has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns and functional differences amongst neurons, we performed single cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. We also specific combinatorial expression pattern of V2R and H2-Mv genes in Gnao1 neurons. These gene expression patterns, along with differential localization of ER chaperones and structural proteins indicate fundamental differences in ER function associated with neuronal differentiation.

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2024-03-11 | GSE247872 | GEO

Transcriptional instability prevents dispersion of functional vomeronasal receptor genes [rat]

Project description:Rodents perceive pheromones via vomeronasal receptors encoded by the Vr and Fpr gene superfamilies. The evolution of these latter is exceptionally dynamic. We report here that high numbers of V1r pseudogenes are scattered in mammalian genomes, contrasting with the clustered organization of functional V1r and Fpr genes. We also found that V1r pseudogenes are more likely to be expressed when located in a functional V1r gene cluster than when isolated. To explore the potential regulatory role played by the association of functional vomeronasal receptor genes with their clusters, we dissociated the mouse Fpr-rs3 from its native cluster via transgenesis. Singular and specific transgenic Fpr-rs3 transcription was observed in young vomeronasal neurons, but was only transient. Our data point to the existence of transcription stabilizing elements not coupled to vomeronasal gene units but rather associated with vomeronasal gene clusters, and thus explain the evolutionary conserved clustered organization of functional vomeronasal genes.

2022-10-02 | GSE190612 | GEO

Transcriptional instability prevents dispersion of functional vomeronasal receptor genes [mouse]

2022-10-02 | GSE190611 | GEO

Transcriptional instability prevents dispersion of functional vomeronasal receptor genes [scRNA-seq]

2022-10-02 | GSE193024 | GEO

Transcriptome of the vomeronasal organ in Vmn2r1 knock out mice

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/

2015-10-20 | E-ERAD-402 | biostudies-arrayexpress

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