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

Lin, Jennifer M.; Taroc, Ed Zandro M.; Frías, Jesús; Prasad, Aparna; Catizone, Allison N; Sammons, Morgan A.; Forni, Paolo E.

doi:10.1016/j.ydbio.2018.06.007

Cited by 33 publications

(72 citation statements)

References 44 publications

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“…To test the effects of Smad4 conditional ablation in maturing basal VSNs, we analyzed the cell composition and maturation state of cells in the VNE at P15. At this stage, we found a small but significant increase in the number of proliferative (Ki67+) cells, which suggests a compensatory response to epithelial cell loss (Lin et al, 2018), ( Fig. 3 A,B,C).…”

Section: Ap-2εcre Driven Smad4 Ablation Shows No Clear Abnormalities mentioning

confidence: 67%

“…However, the reduction in cFos activation in the anterior AOB likely indicates a postsynaptic defect secondary to Smad4 ablation in the mitral cells of the aAOB. In fact, we previously reported that some of the mitral cells of the AOB are positive for AP-2ε lineage (Lin et al, 2018).…”

Section: Exposurementioning

confidence: 93%

“…P-Smad1,5,8 immunostaining showed immunoreactivity in PECAM positive endothelial cells (Fig.1 I) and in VSNs in the basal territories proximal to PECAM+/Col IV+ vessels and basal lamina ( Fig.1 G,H). Using sections from AP-2εCre +/-/R26R lineage traced animals (Lin et al, 2018), where basal cells are genetically traced after AP-2ε expression ( Fig. 1 I), double immunofluorescent staining against p-Smad1,5,8 showed that nearly all basal VSNs were positive for active BMP intracellular signaling beginning at the marginal zone ( Fig.…”

Section: Localization Of Active Bmp Signaling In Basal Vsnsmentioning

confidence: 99%

“…To investigate the role of canonical TGF-β/BMP signaling in differentiating basal VSNs, we exploited AP-2εCre mice as a genetic entry point to conditionally ablate Smad4 flox/flox (Yang et al, 2002) in immature (GAP43+) basal VSNs (Lin et al, 2018). We validated AP-2εCre mediated ablation at postnatal age P15.…”

Section: Conditional Ablation Of Smad4 Disrupts Tgf-β/bmp Signaling Imentioning

confidence: 99%

“…The cell density of basal VSNs significantly increased in Smad4cKO mice compared to controls (+54.72%; p= 0.0017), while no difference in cell density occurred in apical VSNs. We then sought to determine if basal cells in Smad4cKO mice transdifferentiated into apical VSNs (Lin et al, 2018) by performing AP-2εCre +/-/R26R lineage tracing on Smad4 conditional mutants (AP-2εCre +/-/Smad4 flox/flox /R26 YFP+/-). In contrast to the AP-2ε KOs (Lin et al, 2018) these mutants did not show the presence of VSNs that have transdifferentiated from basal to apical VSNs ( Fig.…”

Section: Ap-2εcre Driven Smad4 Ablation Shows No Clear Abnormalities mentioning

confidence: 99%

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Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons

Naik

Lin²,

Taroc³

et al. 2019

Preprint

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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-β/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.

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Section: Ap-2εcre Driven Smad4 Ablation Shows No Clear Abnormalities mentioning

confidence: 67%

Section: Exposurementioning

confidence: 93%

Section: Localization Of Active Bmp Signaling In Basal Vsnsmentioning

confidence: 99%

Section: Conditional Ablation Of Smad4 Disrupts Tgf-β/bmp Signaling Imentioning

confidence: 99%

Section: Ap-2εcre Driven Smad4 Ablation Shows No Clear Abnormalities mentioning

confidence: 99%

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Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons

Naik

Lin²,

Taroc³

et al. 2019

Preprint

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Illuminating the terminal nerve: Uncovering the link between GnRH‐1 neuron and olfactory development

Amato,

Taroc,

Forni

2024

J of Comparative Neurology

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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 OP induce olfactory bulb (OB) morphogenesis. In mice, GnRH‐1 neurons appear in the olfactory system around mid‐gestation and migrate via the TN axons to different brain regions. The GnRH‐1 neurons are crucial in controlling the hypothalamic‐pituitary‐gonadal axis. Kallmann syndrome is characterized by impaired olfactory system development, defective OBs, 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 OB morphogenesis and GnRH‐1 neuronal migration. Prokr2 loss‐of‐function mutations can cause Kallmann syndrome (KS), 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 OB morphogenesis. Single‐cell RNA sequencing identified that the TN is formed by neurons 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.

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Following the p63/Keratin5 basal cells in the sensory and non‐sensory epithelia of the vomeronasal organ

LeFever,

Katreddi,

Dolphin

et al. 2024

Genesis

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SummaryThe vomeronasal organ (VNO) is a part of the accessory olfactory system, which detects pheromones and 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 in cellular structure, receptor expression, and connectivity. The vomeronasal organ of rodents comprises a sensory epithelium (SE) and a thin non‐sensory epithelium (NSE) 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, the MOE also comprises p63 positive horizontal basal cells, a second pool of quiescent stem cells that become active in response to injury. Immunolabeling against the transcription factor p63, Keratin‐5 (Krt5), Krt14, NrCAM, and Krt5Cre tracing experiments highlighted the existence of horizontal basal cells distributed along the basal lamina of SE of the VNO. Single cell sequencing and genetic lineage tracing suggest that the vomeronasal horizontal basal cells arise from basal progenitors at the boundary between the SE and NSE proximal to the marginal zones. Moreover, our experiments revealed that the NSE of rodents is, like the respiratory epithelium, a stratified epithelium where the p63/Krt5+ basal progenitor cells self‐replicate and give rise to the apical columnar cells facing the lumen of the VNO.

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

Cited by 33 publications

References 44 publications

Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons

Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons

Illuminating the terminal nerve: Uncovering the link between GnRH‐1 neuron and olfactory development

Following the p63/Keratin5 basal cells in the sensory and non‐sensory epithelia of the vomeronasal organ

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