ArticlePloS one2015
Ewing sarcoma ewsa protein regulates chondrogenesis of Meckel's cartilage through modulation of Sox9 in zebrafish.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma Proliferation and Migration.Advanced functional materials · 2026Article
- Exploring New Horizons: Advancements in Cartilage Tissue Engineering Under Space Microgravity.Cureus · 2024Review
- Zebrafish crocc2 mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- EWSR1 prevents the induction of aneuploidy through direct regulation of Aurora B.Frontiers in cell and developmental biology · 2023Article
- Hippo-Yap/Taz signalling in zebrafish regeneration.NPJ Regenerative medicine · 2022Review
- Super-enhancer-associated MEIS1 promotes transcriptional dysregulation in Ewing sarcoma in co-operation with EWS-FLI1.Nucleic acids research · 2019Article
- The Hippo pathway effector Taz is required for cell morphogenesis and fertilization in zebrafish.Development (Cambridge, England) · 2018Article
- Kinesin-1 promotes chondrocyte maintenance during skeletal morphogenesis.PLoS genetics · 2017Article
- Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish.Scientific reports · 2016Article
- An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.Stem cell reports · 2016Article
- Correction: Ewing sarcoma Ewsa protein regulates chondrogenesis of Meckel's cartilage through modulation of Sox9 in zebrafish.PloS one · 2015Article
- Chromosomal localization of Ewing sarcoma EWSR1/FLI1 protein promotes the induction of aneuploidy.The Journal of biological chemistryArticle
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Ewing sarcoma is the second most common skeletal (bone and cartilage) cancer in adolescents, and it is characterized by the expression of the aberrant chimeric fusion gene EWS/FLI1. Wild-type EWS has been proposed to play a role in mitosis, splicing and transcription. We have previously shown that EWS/FLI1 interacts with EWS, and it inhibits EWS activity in a dominant manner. Ewing sarcoma is a cancer that specifically develops in skeletal tissues, and although the above data suggests the significance of EWS, its role in chondrogenesis/skeletogenesis is not understood. To elucidate the function of EWS in skeletal development, we generated and analyzed a maternal zygotic (MZ) ewsa/ewsa line because the ewsa/wt and ewsa/ewsa zebrafish appeared to be normal and fertile. Compared with wt/wt, the Meckel's cartilage of MZ ewsa/ewsa mutants had a higher number of craniofacial prehypertrophic chondrocytes that failed to mature into hypertrophic chondrocytes at 4 days post-fertilization (dpf). Ewsa interacted with Sox9, which is the master transcription factor for chondrogenesis. Sox9 target genes were either upregulated (ctgfa, ctgfb, col2a1a, and col2a1b) or downregulated (sox5, nog1, nog2, and bmp4) in MZ ewsa/ewsa embryos compared with the wt/wt zebrafish embryos. Among these Sox9 target genes, the chromatin immunoprecipitation (ChIP) experiment demonstrated that Ewsa directly binds to ctgfa and ctgfb loci. Consistently, immunohistochemistry showed that the Ctgf protein is upregulated in the Meckel's cartilage of MZ ewsa/ewsa mutants. Together, we propose that Ewsa promotes the differentiation from prehypertrophic chondrocytes to hypertrophic chondrocytes of Meckel's cartilage through inhibiting Sox9 binding site of the ctgf gene promoter. Because Ewing sarcoma specifically develops in skeletal tissue that is originating from chondrocytes, this new role of EWS may provide a potential molecular basis of its pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.