Biology subjects

Forni, P. E.

Publications and source records attributed to Forni, P. E..

16 recordsLinked to original sources

bioRxiv2025

GnRH-1 Neurons Are Not in the Goofy Group: 123cre Tracing Sets the Record Straight

The olfactory placode (OP) gives rise to a wide array of chemosensory neurons in the nasal region, including olfactory sensory neurons, vomeronasal sensory neurons, and those of the septal organ and Grueneberg ganglion. During placodal invagination, the OP also produces migratory neurons, including gonadotropin-releasing hormone-1 (GnRH-1) neurons, somatostatin-expressing neurons, Prokineticin Receptor 2 (Prokr2) pioneer/terminal nerve (TN) neurons, which are thought to initiate olfactory bulb development. Despite decades of research, the genetic lineage and molecular identity of OP-derived neuronal types remain under investigation. GnRH-1 neurons play essential roles in reproduction and chemodetection but appear genetically distinct from olfactory and vomeronasal chemosensory neurons. The Golgi-associated olfactory signaling regulator Goofy/Gfy is broadly expressed across the placode-derived nasal chemosensory neurons. To determine whether its expression is specific to nasal chemosensory neurons or it is a shared genetic feature across OP derivatives we characterized Gfy expression and lineage at embryonic and postnatal stages. Our results confirm broad Gfy expression in developing chemosensory neurons and subsets of olfactory pioneer/TN neurons. However, we found that while Gfy was not expressed in GnRH-1 neurons while migrating, analysis at late development and postnatal stages, revealed the existence of Gfy-traced neuronal populations in the basal forebrain, some of which also express GnRH. These findings uncover previously unrecognized genetic heterogeneity among migratory nasal neurons and reinforce previous studies suggesting the existence of additional neurons with nasal origin in the brain. In addition to this, analysis of Gfy expression along the developmental trajectory of vomeronasal sensory neurons at postnatal stages revealed intriguing differences in the developmental dynamics across the two main types of vomeronasal sensory neurons.

developmental biology↗

bioRxiv2025

Canopy1/Cnpy1 is required for proper V2R processing and transport; its loss impairs the function and circuit organization of basal/V2R vomeronasal sensory neurons

The vomeronasal organ (VNO) is a specialized chemosensory structure in the nasal cavity that detects pheromones and mediates social and reproductive behaviors. The VNO of rodents is populated by different types of vomeronasal sensory neurons (VSNs). Apical VSNs, located near the lumen, express the transcription factor (TF) Meis2, V1R family receptors, and the G protein subunit Gao; the VSNs distributed closer to the basal lamina express the TF Tfap2e/AP-2{varepsilon}, V2R receptors, and the G protein subunit Gai2. In addition, sparse cells in the VNO express the Formyl Peptide Receptors (FPRs). Single-cell mRNA sequencing (scRNA Seq) identified over 980 differentially expressed genes between these cell types, with many linked to the endoplasmic reticulum (ER). Among these ER proteins, Canopy1 (Cnpy1), was found to be among the most enriched genes in V2R+ VSNs. Previously studied only in zebrafish, Cnpy1 was found to affect Fgfr1 signaling and is thus also known as "FGF signaling regulator-1". In a previous study, we discovered that AP-2e upregulates Cnpy1 expression. Although Cnpy1 knockout mice are viable and have normal VNO development at birth, they experience a progressive degeneration and loss of V2R-expressing VSNs. Prior to symptoms, the basal VSNs of KO mice display reduced V2R protein immunoreactivity in the soma and a complete absence of the protein at the lumen of the VNO, rendering the neurons non-functional. Cnpy1 KOs exhibit altered guidance cues and adhesion molecule expression, along with disrupted connectivity to the accessory olfactory bulb (AOB). Our study shows that distinct neuronal types depend on unique ER protein repertoires to maintain proper proteostasis. The loss of Cnpy1 highlights the importance of cell-type-specific ER factors in the differentiation and function of specific neurons, revealing mechanisms that drive neuronal diversity and vulnerability to ER gene disruption.

neuroscience↗

bioRxiv2025

Tracing Early Migratory Neurons in the Developing Nose Using Contactin-2 (Cntn2)CreERT2

Neuronal migration during embryonic development is a fundamental process. In the developing nose of rodents, neurons that form during early neurogenic waves in the olfactory placode leave this structure to migrate toward or into the developing brain as part of the migratory mass. This mass includes Gonadotropin-releasing hormone-1 (GnRH-1) neurons, pioneer/terminal nerve (TN) neurons, as well as neural crest-derived olfactory glial cells called olfactory ensheathing cells. There have been a limited number of molecular markers available to effectively trace and functionally manipulate the early migratory neurons that originate in the olfactory region. Contactin-2 (Cntn2), also known as transiently expressed axonal surface glycoprotein-1 (TAG-1), has been used to label various developing neuronal populations, including the commissural neurons of the spinal cord, motor neurons, and TN neurons. Previous single-cell RNA sequencing analyses of the developing olfactory system have identified Cntn2 expression in the TN, suggesting that Cntn2 is a suitable molecular marker for studying nasal migratory neurons. To trace Cntn2 expression in the developing olfactory system, we generated an inducible Cntn2CreERT2 mouse line. In this study, we outline how this mouse line can serve as an effective tool for time-controlled chimeric manipulation of specific neuronal populations of interest.

neuroscience↗

bioRxiv2025

Shared Lineage, Distinct Outcomes: Yap and Taz Loss Differentially Impact Schwann and Olfactory Ensheathing Cell Development Without Disrupting GnRH-1 Migration

Olfactory Ensheathing Cells (OECs) are glial cells originating from the neural crest, critical for bundling olfactory axons to the brain. Their development is crucial for the migration of Gonadotropin-Releasing Hormone-1 (GnRH-1) neurons, which are essential for puberty and fertility. OECs have garnered interest as potential therapeutic targets for central nervous system lesions, although their development is not fully understood. Our single-cell RNA sequencing of mouse embryonic nasal tissues suggests that OECs and Schwann cells share a common origin from Schwann cell precursors yet exhibit significant genetic differences. The transcription factors Yap and Taz have previously been shown to play a crucial role in Schwann cell development. We used Sox10-Cre mice to conditionally ablate Yap and Taz in migrating the neural crest and its derivatives. Our analyses showed reduced Sox10+ glial cells along nerves in the nasal region, altered gene expression of SCs, melanocytes, and OECs, and a significant reduction in olfactory sensory neurons and vascularization in the vomeronasal organ. However, despite these changes, GnRH-1 neuronal migration remained unaffected. Our findings highlight the importance of the Hippo pathway in OEC development and how changes in cranial neural crest derivatives indirectly impact the development of olfactory epithelia.

developmental biology↗

bioRxiv2023

Following the p63/Keratin5 Basal Cells in the Sensory and Non-sensory Epithelia of The Vomeronasal Organ

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 non-sensory 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 of 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.

developmental biology↗

bioRxiv2023

Illuminating the Terminal Nerve: Uncovering the Link between GnRH-1 and Olfactory Development.

During embryonic development, the olfactory placode (OP) generates migratory neurons, including olfactory pioneer neurons, cells of the terminal nerve (TN), Gonadotropin-releasing hormone-1 (GnRH-1) neurons, and other uncharacterized neurons. Pioneer neurons from the olfactory placode induce olfactory bulb morphogenesis. In mice, GnRH-1 neurons appear in the olfactory system around mid-gestation and migrate via the terminal nerve axons to different brain regions. The GnRH-1 neurons are crucial in controlling the hypothalamic-pituitary-gonadal (HPG) axis. Kallmann syndrome is characterized by impaired olfactory system development, defective olfactory bulbs, defective secretion of GnRH-1, and infertility. The precise mechanistic link between the olfactory system and GnRH-1 development remains unclear. Studies in humans and mice highlight the importance of the Prokineticin-2/Prokineticin-Receptor-2 (Prokr2) signaling pathway in olfactory bulb morphogenesis and GnRH-1 neuronal migration. Prokr2 loss-of-function mutations can cause Kallmann syndrome, and hence the Prokr2 signaling pathway represents a unique model to decipher the olfactory/GnRH-1 connection. We discovered that Prokr2 is expressed in the TN neurons during the critical period of GnRH-1 neuron formation, migration, and induction of olfactory bulb morphogenesis. Single-cell RNA sequencing identified that the TN is formed by neurons that are distinct from the olfactory neurons. The TN neurons express multiple genes associated with KS. Our study suggests that the aberrant development of pioneer/TN neurons might cause the KS spectrum. Key Points1) Pioneer or terminal nerve neurons play a crucial role in initiating the development of the olfactory bulbs. We found that the Prokineticin Receptor-2 gene, associated with Kallmann syndrome, is expressed by the olfactory pioneer/terminal nerve neurons. 2) We genetically traced, isolated, and conducted Single-cell RNA sequencing on terminal nerve neurons of rodents. This analysis revealed a significant enrichment of gene expression related to Kallmann syndrome. 3) Our study indicates that the investigation of Pioneer/terminal nerve neurons should be a pivotal focal point for comprehending developmental defects affecting olfactory and GnRH-1 systems.

developmental biology↗

bioRxiv2023

Loss Of Chromodomain of Male-Specific Lethal 3 (MSL3) Does Not Affect Spermatogenesis In Rodents

Msl3 is a member of the chromatin-associated male-specific lethal MSL complex which is responsible for the transcriptional upregulation of genes on the X chromosome in males Drosophila. Although the dosage complex operates differently in mammals, the Msl3 gene is conserved from flies to humans. Msl3 is required for meiotic entry during Drosophila oogenesis. Recent reports indicate that also in primates, Msl3 is expressed in undifferentiated germline cells before meiotic entry. However, if Msl3 plays a role in the meiotic entry of mammals has yet to be explored. To study this, we used mouse spermatogenesis as a study model. Analyses of single cells RNA-seq data revealed that, in mice, Msl3 is mostly expressed in meiotic cells. To test the role of Msl3 in meiosis, we used a male germline-specific Stra8-iCre driver and a newly generated Msl3flox conditional knock-out mouse line. Msl3 conditional loss-of-function in spermatogonia did not cause spermatogenesis defects or changes in the expression of genes related to meiosis. Our data suggest that, in mice, Msl3 exhibits delayed expression compared to Drosophila and primates, and loss-of-function mutations disrupting the chromodomain of Msl3 alone do not impede meiotic entry in rodents.

developmental biology↗

bioRxiv2022

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 vomeronasal sensory neurons (VSNs), and vomeronasal dependent behaviors can be reprogrammed through the rescue of tfap2e/AP-2{varepsilon} expression in the AP-2{varepsilon} mice, and partially reprogrammed by inducing ectopic AP-2{varepsilon} expression in mature apical VSNs. We suggest that the transcription factor AP-2{varepsilon} can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/476379v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@1f8b849org.highwire.dtl.DTLVardef@afe27org.highwire.dtl.DTLVardef@1b3e8d4org.highwire.dtl.DTLVardef@7af3b1_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2021

PDFGRα+ Stromal Cells Promote Salivary Gland Proacinar Differentiation Through FGF2-dependent BMP7 Signaling.

3.0Stromal cells can direct epithelial differentiation during organ development; however, these pathways remain poorly defined. FGF signaling is essential for submandibular salivary gland development, and FGF2 can regulate proacinar cell differentiation in organoids through autocrine signaling in stromal cells. We performed scRNA Seq and identified stromal cell subsets expressing Fgf2 and Fgf10 that also express Pdgfr. When combined with epithelial cells in organoids, MACS-sorted PDGFR+ cells sufficiently promoted proacinar differentiation. Gene expression analysis revealed FGF2 activates the gene Bmp7 in the stroma. BMP7 could replace stromalsignaling and stimulate epithelial acinar differentiation but not branching. However, in the absence of FGF2, pathway analysis revealed that the stromal cells differentiated into myofibroblasts. Myofibroblast differentiation was induced when we treated organoids with TGF{beta}1, which also prevented proacinar differentiation. Conversely, FGF2 reversed TGF{beta}s effects. Dissecting pathways driving acinar differentiation will facilitate development of regenerative therapies. 2.0 Summary StatementEmbryonic salivary glands contain multiple stromal cell populations. FGF2 maintains the stromal Pdgfr+ population in-vitro. The PDGFR+ stromal cells drive early epithelial secretory cell differentiation using BMP7.

developmental biology↗

bioRxiv2021

Notch signaling determines cell-fate specification of the two main types of vomeronasal neurons of rodents.

The ability of terrestrial vertebrates to find food, mating partners and to avoid predators heavily relies on the detection of chemosensory information from the environment. The olfactory system of most vertebrate species comprises two distinct chemosensory systems usually referred to as the main and the accessory olfactory system. Olfactory sensory neurons of the main olfactory epithelium detect and transmit odor information to main olfactory bulb (MOB), while the chemosensory neurons of the vomeronasal organ detect semiochemicals responsible for social and sexual behaviors and transmit information to the accessory olfactory bulb (AOB). The vomeronasal sensory epithelium (VNE) of most mammalian species contains uniform vomeronasal (VN) system with vomeronasal sensory neurons (VSNs) expressing vomeronasal receptors of the V1R family. However, rodents and some marsupials have developed a more complex binary VN system, where VNO containing a second main type of VSNs expressing vomeronasal receptors of the V2R family is identified. In mice, V1R and V2R VSNs form from a common pool of progenitors but have distinct differentiation programs. As they mature, they segregate in different regions of the VNE and connect with different parts of the AOB. How these two main types of VSNs are formed has never been addressed. In this study, using single cell RNA sequencing data, we identified differential expression of Notch1 receptor and Dll4 ligand among the neuronal precursors at the VSN dichotomy. We further demonstrated with loss of function (LOF) and gain of function (GOF) studies that Dll4-Notch1 signaling plays a crucial role in triggering the binary dichotomy between the two main types of VSNs in mice. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=50 SRC="FIGDIR/small/466003v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@2511feorg.highwire.dtl.DTLVardef@1c066e1org.highwire.dtl.DTLVardef@a24c02org.highwire.dtl.DTLVardef@12c5320_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2021

Automated quantification of vomeronasal glomeruli number, size, and color composition after immunofluorescent staining

Glomeruli are neuropil rich regions of the main or accessory olfactory bulbs where the axons of olfactory or vomeronasal neurons and dendrites of mitral/tufted cells form synaptic connections. In the main olfactory system olfactory sensory neurons (OSNs) expressing the same receptor innervate one or two glomeruli. However, in the accessory olfactory system, vomeronasal sensory neurons (VSNs) expressing the same receptor can innervate up to 30 different glomeruli in the accessory olfactory bulb (AOB). Genetic mutation disrupting genes with a role in defining the identity/diversity of olfactory and vomeronasal neurons can alter number and size of glomeruli. Interestingly, two cell surface molecules, Kirrel2 and Kirrel3, have been indicated to play a critical role in the organization of axons into glomeruli in the AOB. Being able to quantify differences in glomeruli features such as number, size or immunoreactivity for specific markers is an important experimental approach to validate the role of specific genes in controlling neuronal connectivity and circuit formation in control or mutant animals. Since the manual recognition and quantification of glomeruli on digital images is a challenging and time-consuming task, we generated a program in Python able to identify glomeruli in digital images and quantify their properties, such as size, number, and pixel intensity. Validation of our program indicates that our script is a fast and suitable tool for high throughput quantification of glomerular features of mouse lines with different genetic makeup.

neuroscience↗

bioRxiv2020

Identifying Isl1 genetic lineage in the developing olfactory system and in GnRH-1 neurons

During embryonic development, symmetric ectodermal thickenings (olfactory placodes) give rise to several cell types that comprise the olfactory system, such as those that form the terminal nerve ganglion (TN), gonadotropin releasing hormone-1 (GnRH-1) neurons and other migratory neurons in rodents. Even though the genetic heterogeneity among these cell types are documented, unidentified cell populations arising from the olfactory placode remain. One candidate to identify placodal derived neurons in the developing nasal area is the transcription factor Isl1, which was recently identified in GnRH-3 neurons of the terminal nerve in fish, as well as expression in neurons of the nasal migratory mass. Here, we analyzed the Isl1 genetic lineage in chemosensory neuronal populations in the nasal area and migratory GnRH-1 neurons in mice using in-situ hybridization, immunolabeling a Tamoxifen inducible Isl1CreERT and a constitutive Isl1Cre knock-in mouse lines. In addition, we also performed conditional Isl1 ablation in developing GnRH neurons. We found Isl1 lineage across non sensory cells of the respiratory epithelium and sustentacular cells of OE and VNO. We identified a population of transient embryonic Isl1+ neurons in the olfactory epithelium and sparse Isl1+ neurons in postnatal VNO. Isl1 is expressed in almost all GnRH neurons and in approximately half of the other neuron populations in the Migratory Mass. However, Isl1 conditional ablation alone does not significantly compromise GnRH-1 neuronal migration or GnRH-1 expression, suggesting compensatory mechanisms. Further studies will elucidate the functional and mechanistic role of Isl1 in development of migratory endocrine neurons.

developmental biology↗

bioRxiv2019

MSL3 coordinates a transcriptional and translational meiotic program in female Drosophila

Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation and meiotic entry are incompletely understood. Set2, which deposits H3K36me3 modifications, is required for differentiation of GSCs during Drosophila oogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (MSL3) and the histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate entry into meiosis in female Drosophila. MSL3 expression is restricted to the mitotic and early meiotic stages of the female germline, where it promotes transcription of genes encoding synaptonemal complex components and a germline enriched ribosomal protein S19 paralog, RpS19b. RpS19b upregulation is required for translation of Rbfox1, a known meiotic cell cycle entry factor. Thus, MSL3 is a master regulator of meiosis, coordinating the expression of factors required for recombination and GSC differentiation. We find that MSL3 is expressed during mouse spermatogenesis, suggesting a conserved function during meiosis.

developmental biology↗

bioRxiv2019

Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons

The accessory olfactory system is a unique model that can give insights on how the neurons can establish and maintain their identity, and connectivity. The vomeronasal organ (VNO) contains two distinct populations of vomeronasal sensory neurons (VSNs) each with specific innervation patterns to the accessory olfactory bulb (AOB). Though morphogenic signals are critical in defining various neuronal populations, the morphogenic signaling profiles that influence each VSN population remains unknown. Here, we found a pronounced BMP signaling gradient within the basal VSNs. By generating Smad4 conditional mutants, we disrupted canonical TGF-{beta}/BMP signaling in maturing basal VSNs and in all mature VSNs. We show that Smad4 loss-of-function in immature basal neurons leads to a progressive loss of basal VSNs, reduced activation of the remnant basal VSNs, and aberrant glomeruli formation in posterior AOB. However, Smad4 ablation in all mature VSNs does not affect neuronal activity nor survival but causes aberrant glomeruli formation only in the posterior AOB. Our study reveals that Smad4 signaling plays a critical role in mediating development, function, and circuit formation of basal VSNs.

developmental biology↗

bioRxiv2019

Gli3 loss-of-function compromises vomeronasal neurogenesis, formation of olfactory ensheathing cells in the nasal mucosa, and GnRH-1 neuronal migration

During mammalian development, gonadotropin-releasing-hormone-1 neurons (GnRH-1ns) migrate from the developing vomeronasal organ (VNO) into the brain asserting control of pubertal onset and fertility. Recent data suggest that correct development of the olfactory ensheathing cells (OEC) is imperative for normal GnRH-1 neuronal migration. However, the full ensemble of molecular pathways that regulate OEC development remains to be fully deciphered. Loss-of-function of the transcription factor Gli3 is known to disrupt olfactory development, however, if Gli3 plays a role in GnRH-1 neuronal development is unclear. By analyzing Gli3 extra-toe mutants (Gli3Xt/Xt), we found that Gli3 loss-of-function compromises the onset of achaete-scute family bHLH transcription factor 1 (Ascl-1) positive vomeronasal progenitors and the formation of OEC in the nasal mucosa. Surprisingly, GnRH-1 neurogenesis was intact in Gli3Xt/Xt mice but they displayed significant defects in GnRH-1 neuronal migration. In contrast, Ascl-1null mutants showed reduced neurogenesis for both vomeronasal and GnRH-1ns but less severe defects in OEC development. These observations suggest that Gli3 is critical for OEC development in the nasal mucosa and subsequent GnRH-1 neuronal migration. However, the non-overlapping phenotypes between Ascl-1 and Gli3 mutants indicate that Ascl-1, while crucial for GnRH-1 neurogenesis, is not required for normal OEC development. Since Kallmann syndrome (KS) is characterized by abnormal GnRH migration, we examined whole exome sequencing data from KS subjects. We identified and validated a GLI3 loss-of-function variant in a KS individual. These findings provide new insights into GnRH-1 and OECs development and demonstrate that human GLI3 mutations contribute to KS etiology.\n\nSignificance statementThe transcription factor Gli3 is necessary for correct development of the olfactory system. However, if Gli3 plays a role in controlling GnRH-1 neuronal development has not been addressed. We found that Gli3 loss-of-function compromises the onset of Ascl1+ vomeronasal progenitors, formation of olfactory ensheathing cells in the nasal mucosa and impairs GnRH-1 neuronal migration to the brain. By analyzing Ascl1 null mutants we dissociated the neurogenic defects observed in Gli3 mutants from lack of olfactory ensheathing cells in the nasal mucosa, moreover, we discovered that Ascl1 is necessary for GnRH-1 ontogeny. Analyzing human whole exome sequencing data, we identified a GLI3 loss-of-function variant in a KS individual. Our data suggest that GLI3 is a candidate gene contributing to KS etiology.

developmental biology↗

bioRxiv2018

The transcription factor Tfap2e/AP-2ε plays a pivotal role in maintaining the identity of basal vomeronasal sensory neurons

The identity of individual neuronal cell types is defined by the expression of specific combinations of transcriptional regulators that control cell type-specific genetic programs. The epithelium of the vomeronasal organ of mice contains two major types of vomeronasal sensory neurons (VSNs): 1) the apical VSNs which express vomeronasal 1 receptors (V1r) and the G-protein subunit Gi2 and; 2) the basal VSNs which express vomeronasal 2 receptors (V2r) and the G-protein subunit Gao. Both cell types originate from a common pool of progenitors and eventually acquire apical or basal identity through largely unknown mechanisms.\n\nThe transcription factor AP-2{varepsilon}, encoded by the Tfap2e gene, plays a role in controlling the development of GABAergic interneurons in the main and accessory olfactory bulb (AOB), moreover AP-2{varepsilon} has been previously described to be expressed in the VSNs. Here we show that AP-2{varepsilon} is expressed in postmitotic VSNs after they commit to the basal differentiation program. Loss of AP-2{varepsilon} function resulted in reduced number of basal VSNs and in an increased number of neurons expressing markers of the apical lineage. Our work suggests that AP-2{varepsilon}, which is expressed in late phases of differentiation, is not needed to initiate the apical-basal differentiation dichotomy but for maintaining the basal VSNs identity by preventing the expression of apical genes. Moreover, our data suggest that differentiated VSNs of mice retain a notable level of plasticity.\n\nHighlightsO_LIThe VNO contains two major cell types that are segregated in apical and basal regions of the VNO\nC_LIO_LIAP-2{varepsilon} is expressed in postmitotic basal vomeronasal sensory neurons.\nC_LIO_LIAP-2{varepsilon} is essential to maintain the identity of basal vomeronasal sensory neurons.\nC_LI

developmental biology↗