YAP and TAZ loss of function in the neural crest broadly affects olfactory ensheathing cells, olfactory-vomeronasal neurons, but not GnRH-1 neuronal migration.
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PROVIDER: PRJNA1209792 | ENA |
REPOSITORIES: ENA
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Project description:Olfactory Ensheathing Cells (OECs) originate from the neural crest and are critical for bundling olfactory axons to the brain. Their development is vital for the migration of Gonadotropin-Releasing Hormone-1 (GnRH-1) neurons, which are essential for puberty and fertility. OECs are of particular interest for potential treatments of central nervous system lesions, though 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 (SCPs). However, OECs and SCs have significant genetic differences. Wnt1 is highly expressed in pre-migratory neural crest cells, while Sox10 expression occurs later and is lost in most derivatives, except for nasal cartilage, SCPs, SCs, melanocytes, and OECs. Rosa26 lineage tracing revealed that the Wnt1Cre2 mouse line recombines extensively in non-neural crest-derived tissues, while Sox10 Cre more selectively recombines in neural crest derivatives. We used Sox10 Cre mice to manipulate the Yap and Taz genes in migrating neural crest cells. Our analyses showed reduced Sox10+ cells in the nasal region and alterations in gene expression of SCs, melanocytes, and OECs. However, GnRH-1 neuronal migration remained unaffected. Notably, the loss of Yap and Taz in neural crest derivatives led to significant secondary effects in olfactory structures, reducing both olfactory sensory neurons and vascularization in the vomeronasal organ (VNO). Our findings highlight the importance of the Hippo pathway in OEC development and its implications for the olfactory vasculature.
2025-07-15 | GSE286491 | GEO
Project description:Olfactory ensheathing cells are one of the few central nervous system regenerative cells discovered so far. It is characterized by its lifelong nerve regeneration function, and it can also release a variety of neurotrophic factors and neural adhesion molecules. It is considered to be the glial cell with the strongest myelination ability. Olfactory ensheathing cells and Schwann cells have phenotypes in common, they can promote axon regeneration(R. Doucette, 1995). Olfactory ensheathing cells have the characteristics of Schwann cells and astrocytes, but the overall performance tends to be the former, which has two unique characteristics. First, it exists not only in the peripheral nerves (Schwann cells), but also in the central nervous system (astroglia); second, the olfactory mucosa has the ability to regenerate life-long, including human olfactory ensheathing cells(J. C. Bartolomei and C. A. Greer, 2000). Regeneration is a process in which olfactory ensheathing cells participate in efficient regulation, although the specific mechanism is not yet clear. Olfactory ensheathing cells are different from astrocytes and Schwann cells, but at the same time have the characteristics of these two cells(S. C. Barnett, 2004), like Schwann cells help axon growth, but more than Schwann cells It can make axons grow long distances, that is, it has stronger migration(A. Ramon-Cueto et al., 1998); there are also astrocytes that have a nutritional effect on the survival of neurons and the growth of axons, but olfactory ensheathing cells can also wrap neurons forms myelin sheath to support the growth of nerve processes(R. Devon and R. Doucette, 1992; J. Gu et al., 2019). There are two characteristics that make olfactory ensheathing cells the best choice for the treatment of neurological diseases(S. C. Chiu et al., 2009; J. Kim et al., 2018; M. Abdel-Rahman et al., 2018). Olfactory ensheathing cells are gradually used to treat spinal cord injuries and have shown amazing effects(J. C. Bartolomei and C. A. Greer, 2000; K. J. Liu et al., 2010; R. Yao et al., 2018). Olfactory ensheathing cells that have been used in research are usually derived from the olfactory bulb(E. H. Franssen et al., 2007), but it is easier to obtain olfactory ensheathing cells from the olfactory mucosa in clinical practice(M. Ryszard et al., 2006), so the difference between the olfactory ensheathing cells from the olfactory bulb and the olfactory mucosa There are more and more studies(B. M. U. et al., 2007), and previous studies have shown that they not only have many similar functions, but also have many differences(M. W. Richter et al., 2005; L. Wang et al., 2014; K. E. Smith et al., 2020). Because olfactory ensheathing cells derived from the olfactory bulb are not easy to obtain, olfactory ensheathing cells derived from the olfactory mucosa have become the focus of attention. Although we know that olfactory ensheathing cells from two sources have nerve repair functions, it is not clear why the two different sources of olfactory ensheathing cells have different therapeutic effects. Nicolas G. once studied that the genetic difference between the two cells and found that there are many genes related to wound repair and nerve regeneration(G. Nicolas et al., 2010). We have reason to guess that olfactory ensheathing cells from these two sources will also have a large difference in protein level. Our research group wants to use the current mature transcriptome and proteomic sequencing technologies to explore the difference between olfactory ensheathing cells from the olfactory bulb and olfactory mucosa, and explain why the two sources of olfactory ensheathing cells shows different therapeutic effects, hope to provide a new theoretical basis for future clinical treatment.
2022-02-16 | PXD024046 | Pride
Project description:The aim of this study was to use global gene expression profiling to define intrinsic molecular differences that distinguish olfactory ensheathing cells from mucosa (OM-OECs) from olfactory ensheathing cells from olfactory bulb (OB-OECs). 10,000 OECs from olfactory mucosa (OM) or olfactory bulb (OB) were isolated from 4 rats.
2009-12-02 | GSE19250 | GEO
Project description:Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are central regulators of fertility and integrate endogenous hormonal status with environmental cues to ensure reproductive success. Here, we found that extra-hypothalamic GnRH neurons in the olfactory bulb of adult mice and humans (GnRHOB) can mediate social recognition. We show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the hypothalamic median eminence. We demonstrate that male GnRHOB neurons express vomeronasal and olfactory receptors, are activated by female odors in vivo, and mediate gonadotropin release in response to female urine. We find that male preference for female odors is enhanced upon chemogenetic activation of GnRHOB neurons and is impaired after genetic inhibition or ablation of these cells and relies on GnRH signaling in the posterodorsal medial amygdala. Taken together, these results establish GnRHOB neurons as a central regulatory hub regulating fertility, sex recognition, and mating in males.
2024-06-17 | GSE268138 | GEO
Project description: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)+ 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 nonoverlapping phenotypes between Ascl-1 and Gli3 mutants indicate that Ascl-1, while crucial for GnRH-1 neurogenesis, is not required for normal OEC development. Because Kallmann syndrome (KS) is characterized by abnormal GnRH-1ns 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.SIGNIFICANCE STATEMENT The 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 Ascl-1+ vomeronasal progenitors, formation of olfactory ensheathing cells in the nasal mucosa, and impairs GnRH-1 neuronal migration to the brain. By analyzing Ascl-1null mutants we dissociated the neurogenic defects observed in Gli3 mutants from lack of olfactory ensheathing cells in the nasal mucosa, moreover, we discovered that Ascl-1 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.
| S-EPMC6948949 | biostudies-literature
Project description:Infection-induced aversion against enteropathogens is a conserved sickness behavior that can promote host survival1-3. The etiology of this behavior remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviors against toxic microbes4-6. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviors remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfactory perception through metabolic reprogramming of ensheathing glia of the antennal lobe. This reprogramming depends on JAK/STAT signaling activation in ensheathing glia as a consequence of infection-induced Unpaired cytokine expression in the intestine. JAK/STAT signaling induces the expression of glial monocarboxylate transporters (MCTs) and the apolipoprotein glial lazarillo (Glaz), resulting in changes in glial lipid metabolism. This modulates olfaction sensitivity, promoting avoidance of bacteria-laced food and increasing animal survival. While transient in young animals, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old animals due to age-related intestinal inflammation, contributing to an age-related decline in olfaction sensitivity. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism causing lasting changes in neuronal activity in the aging animal.
2021-06-02 | GSE168530 | GEO
Project description:During embryonic development, the olfactory placode (OP) gives rise to various populations of neurons; these include putative olfactory pioneer neurons, different neurons of unknown identity and function, cells of the terminal nerve, and the Gonadotropin-releasing hormone-1 (GnRH-1) neurons. In mice, the GnRH-1 neurons are first detectable in the developing olfactory system around mid-gestation. From here, the GnRH-1 neurons migrate, along the axons of the terminal nerve (TN), to various regions of the developing brain. Once in the brain, the GnRH-1 neurons play a central role in controlling the hypothalamic-pituitary-gonadal (HPG) axis. Early migratory neurons forming from the olfactory placode have been proposed to play a vital role in inducing olfactory bulb morphogenesis. Kallmann syndrome is a condition characterized by defective development of the olfactory system and infertility. Murine studies have demonstrated the critical role of the Prokineticin 2-Prokinteicin Receptor 2 pathway in olfactory bulb morphogenesis and GnRH-1 neuronal migration. Loss-of-function Prokr2 mutations cause both Kallmann syndrome associated with bulb agenesis and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Following Prokr2 expression and lineage tracing, we found that Prokr2 is not expressed by the cells of the developing olfactory bulb but by migratory putative pioneer/terminal nerve neurons. Performing single-cell-RNA-sequencing, we identified genes enriched in the migratory cells of the putative terminal nerve. By integrating genetic lineage tracing and single-cell transcriptomics, we identified previously undescribed populations of migratory neurons that appear to be enriched in the expression of several genes related to olfactory defects, GnRH migratory deficiencies and infertility.
2024-03-11 | GSE234871 | GEO
Project description:Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridisation, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific, i.e., not expressed by Schwann cells. One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.
2020-06-02 | GSE138596 | GEO
Project description:Olfactory ensheathing cells (OECs) are the only glial cells that support the olfactory sensory neurons which undergo adult neurogenesis and continually project their axons to glomeruli in the olfactory bulbs. We used single cell RNA sequencing to study the gene expression programs of OECs and to determine the diversity of purified OECs previously shown to promote spinal cord injury repair. Our analyses revealed five subtypes of OECs, each expressing unique marker genes and pathways indicative of progenitor, axonal regeneration, migration, or microglia-like functions. As expected, we found substantial overlap of OEC genes with those of Schwann cells, but also with astrocytes, oligodendrocytes and microglia. We experimentally confirmed the classic marker genes of the OEC subtypes and provide evidence that Reelin and Connective Tissue Growth Factors are secreted by multiple OEC subtypes. Our results support that adult OECs are a hybrid glia including some with progenitor characteristics and that they likely carry out diverse functions related to injury repair and axonal regeneration.
2022-10-13 | GSE215247 | GEO
Project description:We used microarrays to detail the global program of gene expression underlying gonadotropin-releasing hormone (GnRH) generation and delamination from the olfactory placode.
2016-09-30 | GSE87486 | GEO