TGF-β1-induced m6A modifications accelerate onset of nuclear cataract in high myopia by influencing the PCP pathway [meRIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE244037 | GEO | 2025/02/12
REPOSITORIES: GEO
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Project description:Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation. We have compared gene expression of ocular lenses of mice that are lens specific conditional mutants of Notch2 gene to that of littermate controls that had no ablation of Notch2 gene in the lens. Two lenses of each of the three conditional mutants and controls were pooled together and total RNA was harvested from embryonic day 19.5 (E19.5) lenses. Gene expression changes caused by absence of Notch2 gene in the lens were analyzed.
2011-12-31 | E-GEOD-31643 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from Tdrd7 knockdown cells compared to lentiviral GFP control in 21EM15 lens epithelial-derived cell line
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Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from P30 Lens from Tdrd7 null mice compared to that of Tdrd7 heterozygous mice.
2012-02-21 | E-GEOD-25776 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from P4 Lens from Tdrd7 null mice compared to that of Tdrd7 heterozygous mice.
2012-02-21 | E-GEOD-25775 | biostudies-arrayexpress
Project description:Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation.
2011-12-31 | GSE31643 | GEO
Project description:Despite strong evidence that normal lens development and function requires regulation governed by miRNAs, the role of specific miRNAs in mammalian lens FEV development and homeostasis remains largely unexplored. Here we undertook a comprehensive RNA-seq analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance. We then selected the three most abundant lens miRNAs: miR-184, miR-1 and miR-26 for functional analysis. Of these three miRNAs, only miR-1, which was highly expressed in lens fiber cells, exhibited significant differential expression. Mouse lenses lacking miR-184, or both copies of miR-1, or all three copies of miR-26 exhibited morphologically normal prenatal lens development. However, mice lacking all three copies of miR-26 (miR-26KO) developed postnatal cataracts at approximately 4-6 weeks of age. RNA-seq analysis of neonatal lenses from miR-26KO mice demonstrated a deregulation of the complement pathway, inflammation and epithelial to mesenchymal transition
2024-05-08 | GSE252611 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25776 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25775 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25774 | GEO
Project description:Disruption of the mouse gene encoding the gap junction subunit alpha3 connexin 46 (Cx46) results in the formation of lens cataracts. The timing of the onset of this lens opacity is affected by the genetic background, i.e. the mouse strain. To elucidate the mechanism by which cataracts form in the 129Sv/Jae strain earlier than in the C57BL/6J strain, global gene expression was quantitated in the lenses of these strains. Lens cDNAs were analyzed by hybridization to DNA microarrays and with real time-PCR. Theories are proposed based on the observed higher level of expression of the stress-response genes in the C57BL/6J strain and variations in the expression levels of genes involved in protein synthesis, metabolism, catabolism and cell proliferation. How these variations in gene expression might affect the response of lens fiber cells to the increased calcium, caused by lack of alpha3Cx46, is considered. The possibility that the proteins coded by the strain-variable genes might influence the cataract-associated proteolysis of gamma-crystallin is also addressed. Keywords: Lens, cataract, microarray, connexin 46, gene knock out
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