Cartilage development requires the function of Estrogen-related receptor alpha that directly regulates sox9 expression in zebrafish

Kim, Yong‐Il; Lee, Joon No; Bhandari, Sushil; Nam, In-Koo; Yoo, Kyeong-Won; Kim, Se-Jin; Oh, Gi‐Su; Kim, Hyungjin; So, Hong-Seob; Choe, Seong-Kyu; Park, Raekil

doi:10.1038/srep18011

Cited by 26 publications

(20 citation statements)

References 23 publications

(34 reference statements)

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“…Given that Slc25a17 acts as a potential peroxisomal transporter of essential cofactors such as CoA, FAD, and NAD + , we reasoned that Slc25a17 might play a crucial role in peroxisome number and function. We found that the number of peroxisomes had not changed by slc25a17 knockdown, as similar levels of the peroxisome‐targeted RFP signals between control and MO slc25a17 ‐injected Tg ( ef1α:RFP‐SKL ) transgenic embryos were detected (Figure c; Kim et al, ). To examine peroxisome‐dependent functions involved in the oxidation of very long‐chain fatty acids and the synthesis of ether phospholipids (also known as plasmalogens), we analyzed the expression of genes involved in fatty acid oxidation or plasmalogen synthesis.…”

Section: Resultssupporting

confidence: 54%

“…Control, and slc25a17 or slc25a17l knockdown embryos were collected at various developmental stages, fixed in 4% paraformaldehyde, and processed for in situ hybridization or immunostaining as previously described (Kim et al, ). For immunostaining, antibodies to detect acetylated tubulin (antiacetyl tubulin, 1:500, Sigma‐Aldrich), peroxisomal PMP70 (anti‐PMP70, 1:500, Abcam, Cambridge, United Kingdom), and secondary Alexa Fluor‐conjugated antimouse antibodies (1:400, Invitrogen) or antirabbit (1:400, Invitrogen) antibodies were used.…”

Section: Methodsmentioning

confidence: 99%

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Slc25a17 acts as a peroxisomal coenzyme A transporter and regulates multiorgan development in zebrafish

Kim

Nam

Lee

et al. 2019

Journal Cellular Physiology

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Slc25a17 is known as a peroxisomal solute carrier, but the in vivo role of the protein has not been demonstrated. We found that the zebrafish genome contains two slc25a17 genes that function redundantly, but additively. Notably, peroxisome function in slc25a17 knockdown embryos is severely compromised, resulting in an altered lipid composition. Along the defects found in peroxisome-associated phenotypic presentations, we highlighted that development of the swim bladder is also highly dependent on Slc25a17 function. As Slc25a17 showed substrate specificity towards coenzyme A (CoA), injecting CoA, but not NAD + , rescued the defective swim bladder induced by slc25a17 knockdown. These results indicated that Slc25a17 acts as a CoA transporter, involved in the maintenance of functional peroxisomes that are essential for the development of multiple organs during zebrafish embryogenesis. Given high homology in protein sequences, the role of zebrafish Slc25a17 may also be applicable to the mammalian system. K E Y W O R D S coenzyme A transporter, peroxisomes, solute carrier family 25 member 17, swim bladder, zebrafish

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Section: Resultssupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Slc25a17 acts as a peroxisomal coenzyme A transporter and regulates multiorgan development in zebrafish

Kim

Nam

Lee

et al. 2019

Journal Cellular Physiology

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“…All experiments were approved by the Gwangju Institute of Science and Technology Animal Care and Use Committee. Experimental OA was induced in 10-week-old male mice by DMM surgery, or by IA injection (once weekly for 3 weeks) of adenovirus (1 × 10 9 plaque-forming units [PFUs] in a total volume of 10 μl) expressing ERRγ (Ad- Esrrg ), ERRα (Ad- Esrra ), ZIP8 (Ad- Slc39a8 ), or HIF-2α (Ad- Epas1 ) 10 – 13 , 29 . Where indicated, male mice of various ages (8, 12, 16, and 20 weeks old) were used for experimental OA studies.…”

Section: Methodsmentioning

confidence: 99%

“…The roles of ERRs in cartilage biology are beginning to be investigated, with most studies focusing on the functions of ERRα 26 . For instance, studies have shown that ERRα activates the Sox9 promoter in a rat chondrogenic cell line 27 and rat mandibular condylar chondrocytes 28 , and is required for cartilage development in zebra fish 29 . In contrast, cartilage-specific ERRγ transgenic (Tg) mice exhibit chondrodysplasia, in which repressed chondrocyte proliferation decreases the proliferative zone of the growth plate and reduces bone length 30 .…”

Section: Introductionmentioning

confidence: 99%

Estrogen-related receptor γ causes osteoarthritis by upregulating extracellular matrix-degrading enzymes

et al. 2017

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The estrogen-related receptor (ERR) family of orphan nuclear receptor is composed of ERRα, ERRβ, and ERRγ, which are known to regulate various isoform-specific functions under normal and pathophysiological conditions. Here, we investigate the involvement of ERRs in the pathogenesis of osteoarthritis (OA) in mice. Among ERR family members, ERRγ is markedly upregulated in cartilage from human OA patients and various mouse models of OA. Adenovirus-mediated overexpression of ERRγ in mouse knee joint or transgenic expression of ERRγ in cartilage leads to OA. ERRγ overexpression in chondrocytes directly upregulates matrix metalloproteinase (MMP)-3 and MMP13, which are known to play crucial roles in cartilage destruction in OA. In contrast, genetic ablation of Esrrg or shRNA-mediated downregulation of Esrrg in joint tissues abrogates experimental OA in mice. Our results collectively indicate that ERRγ is a novel catabolic regulator of OA pathogenesis.

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“…Zebrafish has two homologues of sox9, sox9a and sox9b. Both Sox9a and Sox9b play roles on neural, cardiac, and cartilage development Zebrafish [60][61][62][63][64] . Network analysis showed that many of these dysregulated transcription factors interact with each other, which suggests that the ethanol-induced developmental defects were the combined and perhaps synergistic effects of multiple regulators and that manipulation of one gene would not lead to complete rescue of ethanol-induced defects.…”

Section: Discussionmentioning

confidence: 99%

Embryonic ethanol exposure alters expression of sox2 and other early transcripts in zebrafish, producing gastrulation defects

Sarmah

Srivastava

McClintick

et al. 2020

Sci Rep

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Ethanol exposure during prenatal development causes fetal alcohol spectrum disorder (FASD), the most frequent preventable birth defect and neurodevelopmental disability syndrome. The molecular targets of ethanol toxicity during development are poorly understood. Developmental stages surrounding gastrulation are very sensitive to ethanol exposure. To understand the effects of ethanol on early transcripts during embryogenesis, we treated zebrafish embryos with ethanol during pre-gastrulation period and examined the transcripts by Affymetrix GeneChip microarray before gastrulation. We identified 521 significantly dysregulated genes, including 61 transcription factors in ethanol-exposed embryos. Sox2, the key regulator of pluripotency and early development was significantly reduced. Functional annotation analysis showed enrichment in transcription regulation, embryonic axes patterning, and signaling pathways, including Wnt, Notch and retinoic acid. We identified all potential genomic targets of 25 dysregulated transcription factors and compared their interactions with the ethanol-dysregulated genes. This analysis predicted that Sox2 targeted a large number of ethanoldysregulated genes. A gene regulatory network analysis showed that many of the dysregulated genes are targeted by multiple transcription factors. Injection of sox2 mRNA partially rescued ethanol-induced gene expression, epiboly and gastrulation defects. Additional studies of this ethanol dysregulated network may identify therapeutic targets that coordinately regulate early development.Fetal alcohol spectrum disorder (FASD) is caused by the exposure to ethanol during prenatal developmental 1-3 . FASD patients display a range of morphological deformities and neurological deficits, including characteristic craniofacial dysmorphology, cognitive impairment, sensory defects, motor disabilities and organ deformities. A recent meta-analysis of FASD among children and youth showed the prevalence is approximately 0.8% globally, but it exceeds 1% in 76 countries 4 . The World Health Organization (WHO) European Region has the highest prevalence of FASD (1.98%) followed by the WHO Region of Americas (0.88%) 4 . Among all the countries studied to date, FASD is the most prevalent in South Africa where the prevalence is as high as 11.1% 4 . FASD prevalence is notably higher among special populations, for example, low socioeconomic status populations 5,6 , children in orphanages, people in psychiatric care etc. 4 .Despite various proposed mechanisms to explain FASD etiology, the molecular targets of ethanol toxicity during development are poorly understood. Conception through gastrulation are sensitive periods for ethanol-induced defects 7,8 . During this period stem and progenitor cells transition from pluripotency to one of the three germ layers, and the cells undergo coordinated movements to organize the body plan 9,10 . These effects are regulated transcriptionally, for example, through the maternal to zygotic transition and the pluripotency transcriptional circuit. S...

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Cartilage development requires the function of Estrogen-related receptor alpha that directly regulates sox9 expression in zebrafish

Cited by 26 publications

References 23 publications

Slc25a17 acts as a peroxisomal coenzyme A transporter and regulates multiorgan development in zebrafish

Slc25a17 acts as a peroxisomal coenzyme A transporter and regulates multiorgan development in zebrafish

Estrogen-related receptor γ causes osteoarthritis by upregulating extracellular matrix-degrading enzymes

Embryonic ethanol exposure alters expression of sox2 and other early transcripts in zebrafish, producing gastrulation defects

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