In Drosophila, the 'Notch' gene controls differentiation to various cell fates in many tissues. Three mammalian 'Notch'
homologs have been identified. All 3 are very highly conserved relative to the Drosophila gene, which suggests that
they are important for cell differentiation in mammals. 'Delta' and 'Jagged' are Notch ligands .
General function
Receptor
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Cellular localization
Plasma membrane
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Ovarian function
Follicle development
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Expression regulated by
mir
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Characterization of microRNA profile in human cumulus granulosa cells: identification of microRNAs that regulate Notch signaling and are associated with PCOS. Xu B et al. (2015) Polycystic ovary syndrome (PCOS), a complex and heterogeneous endocrine condition, is characterized by polycystic ovaries, hyperandrogenism, insulin resistance and chronic anovulation. Cumulus granulosa cells surrounding the oocyte are involved in different aspects of PCOS pathology. Several studies suggested that miRNAs play an important regulatory role at the post-transcriptional level in cumulus granulosa cells. Our objective was to describe the altered miRNA expression profiles and miRNA targeted signaling pathways in PCOS. Case-control study that involved 21 women with PCOS and 20 women without the disease (controls).The miRNA expression profiles of human cumulus granulosa cells were determined using next generation sequencing by Illumina Hiseq 2000. The differentially expressed miRNAs and novel miRNAs were validated by quantitative real-time PCR. The Notch3 and MAPK3 were demonstrated to be targeted by miR-483-5p based on quantitative real-time PCR, western blot and luciferase activity assay. Compared to controls, a total of 59 known miRNA were identified that differentially expressed in PCOS cumulus granulosa cells, including 21 miRNAs increase and 38 miRNAs decrease. Moreover, the novel miRNAs were predicted in PCOS and control cumulus granulosa cells. The potential regulating roles of miRNA in pathophysiology of PCOS were analyzed by GO and KEGG pathway annotation, and several important processes were identified to be targeted by the differentially expressed miRNAs, such as Notch signaling, regulation of hormone, and energy metabolism. Furthermore, Notch3 and MAPK3, the members of Notch signalling and ERK-MAPK pathway, were demonstrated to be regulated by miR-483-5p based on negative expression correlation validation and detection of Notch3/MAPK3 expression after miR-483-5p mimics transfection. Dual luciferase activity assay suggested that Notch3 and MAPK3 were directly targeted by miR-483-5p. Our data suggested that miRNAs and their targeted pathways (e.g. Notch signaling pathway) play important roles in the etiology and pathophysiology of PCOS, and provides novel candidates for molecular biomarkers or treatment targets in the research of female infertility associated to PCOS.//////////////////
Ovarian localization
Granulosa
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Johnson J,et al reported that Notch pathway genes are expressed in mammalian ovarian
follicles.
Genes that regulate the proliferation and differentiation of
granulosa cells are beginning to be elucidated. In this study, the expression
patterns of Notch receptor genes and their ligands, which have been shown to
regulate cell-fate decisions in many systems during development, were examined
in the mammalian ovary. In situ hybridization data showed that Notch2, Notch3,
and Jagged2 were expressed in an overlapping pattern in the granulosa cells of
developing follicles. Jagged1 was expressed in oocytes exclusively. Downstream
target genes of Notch also were expressed in granulosa cells. These data
implicate the Notch signaling pathway in the regulation of mammalian
folliculogenesis.