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1.
BMC Genomics ; 19(1): 731, 2018 Oct 05.
Article in English | MEDLINE | ID: mdl-30290792

ABSTRACT

BACKGROUND: The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD. RESULTS: We used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryos were enriched for functions associated to neural development, while up-regulated genes in KO-NTD embryos were enriched for functions related to lipid metabolism. Feeding pregnant dams a vitamin E-enriched diet, which prevents NTD in SR-B1 KO embryos, resulted in mRNA levels for those differentially expressed genes that were more similar to KO-N than to KO-NTD embryos. We used gene regulatory network analysis to identify putative transcriptional regulators driving the different embryonic expression profiles, and identified a regulatory circuit controlled by the androgen receptor that may contribute to this dichotomous expression profile in SR-B1 embryos. Supporting this possibility, the expression level of the androgen receptor correlated strongly with the expression of several genes involved in neural development and lipid metabolism. CONCLUSIONS: Our analysis shows that normal and defective embryos lacking SR-B1 have divergent expression profiles, explained by a defined set of transcription factors that may explain their divergent phenotype. We propose that distinct expression profiles may be relevant during early development to support embryonic nutrition and neural tube closure.


Subject(s)
CD36 Antigens/deficiency , CD36 Antigens/genetics , Gene Expression Profiling , Gene Knockout Techniques , Gene Regulatory Networks , Neural Tube/embryology , Transcription, Genetic , Animals , Humans , Mice , Neural Tube/metabolism , Neural Tube Defects/genetics , Neural Tube Defects/metabolism , Phenotype , Weaning
2.
Sci Rep ; 7(1): 5182, 2017 07 12.
Article in English | MEDLINE | ID: mdl-28701710

ABSTRACT

SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the bidirectional transport of lipids, such as cholesterol and vitamin E, between these particles and cells. During early development, SR-BI is expressed in extraembryonic tissue, specifically in trophoblast giant cells in the parietal yolk sac. We previously showed that approximately 50% of SR-BI-/- embryos fail to close the anterior neural tube and develop exencephaly, a perinatal lethal condition. Here, we evaluated the role of SR-BI in embryonic vitamin E uptake during murine neural tube closure. Our results showed that SR-BI-/- embryos had a very low vitamin E content in comparison to SR-BI+/+ embryos. Whereas SR-BI-/- embryos with closed neural tubes (nSR-BI-/-) had high levels of reactive oxygen species (ROS), intermediate ROS levels between SR-BI+/+ and nSR-BI-/- embryos were detected in SR-BI-/- with NTD (NTD SR-BI-/-). Reduced expression of Pax3, Alx1 and Alx3 genes was found in NTD SR-BI-/- embryos. Maternal α-tocopherol dietary supplementation prevented NTD almost completely (from 54% to 2%, p < 0.001) in SR-BI-/- embryos and normalized ROS and gene expression levels. In sum, our results suggest the involvement of SR-BI in the maternal provision of embryonic vitamin E to the mouse embryo during neural tube closure.


Subject(s)
CD36 Antigens/deficiency , Embryonic Development , Neural Tube/embryology , Neural Tube/metabolism , Vitamin E/metabolism , Animals , Biomarkers , Dietary Supplements , Embryonic Development/genetics , Gene Expression Regulation, Developmental , Mice , Mice, Knockout , Oxidation-Reduction , Yolk Sac/embryology , Yolk Sac/metabolism , alpha-Tocopherol/administration & dosage
3.
Sci Rep ; 6: 25507, 2016 05 05.
Article in English | MEDLINE | ID: mdl-27145700

ABSTRACT

The sensory neurons in the olfactory epithelium (OSNs) are equipped with a large repertoire of olfactory receptors and the associated signal transduction machinery. In addition to the canonical OSNs, which express odorant receptors (ORs), the epithelium contains specialized subpopulations of sensory neurons that can detect specific information from environmental cues and relay it to relevant neuronal circuitries. Here we describe a subpopulation of mature OSNs in the main olfactory epithelium (MOE) which expresses CD36, a multifunctional receptor involved in a series of biological processes, including sensory perception of lipid ligands. The Cd36 expressing neurons coexpress markers of mature OSNs and are dispersed throughout the MOE. Unlike several ORs analyzed in our study, we found frequent coexpression of the OR Olfr287 in these neurons, suggesting that only a specific set of ORs may be coexpressed with CD36 in OSNs. We also show that CD36 is expressed in the cilia of OSNs, indicating a possible role in odorant detection. CD36-deficient mice display no signs of gross changes in the organization of the olfactory epithelium, but show impaired preference for a lipid mixture odor. Our results show that CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction.


Subject(s)
CD36 Antigens/genetics , GTP-Binding Protein alpha Subunits/genetics , Olfactory Marker Protein/genetics , Olfactory Mucosa/metabolism , Olfactory Receptor Neurons/metabolism , Receptors, Odorant/genetics , Animals , CD36 Antigens/deficiency , Cilia/drug effects , Cilia/metabolism , GTP-Binding Protein alpha Subunits/metabolism , Gene Expression Regulation , Lipids/pharmacology , Male , Mice , Mice, Knockout , Odorants/analysis , Olfactory Marker Protein/metabolism , Olfactory Mucosa/cytology , Olfactory Receptor Neurons/cytology , Olfactory Receptor Neurons/drug effects , Pheromones/pharmacology , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptors, Odorant/metabolism , Smell/physiology
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