4.7 Article

Ependymoma associated protein Zfta is expressed in immature ependymal cells but is not essential for ependymal development in mice

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SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-022-05526-y

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  1. Spanish Ministry of Science, Innovation and Universities [PCI2018093062]
  2. Japan Society for the Promotion of Science
  3. Kato Memorial Bioscience Foundation
  4. Mochida Memorial Foundation for Medical and Pharmaceutical Research
  5. Research Foundation for Pharmaceutical Sciences
  6. SGH Foundation
  7. Takeda Science Foundation
  8. Yasuda Memorial Medical Foundation

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This study found the peak expression of ZFTA in mouse embryos and observed that ZFTA may be regulated by ciliary transcription factors. However, ZFTA is not essential for the development or flow of supratentorial ependymoma.
The fusion protein of uncharacterised zinc finger translocation associated (ZFTA) and effector transcription factor of tumorigenic NF-kappa B signalling, RELA (ZFTA-RELA), is expressed in more than two-thirds of supratentorial ependymoma (ST-EPN-RELA), but ZFTA's expression profile and functional analysis in multiciliated ependymal (E1) cells have not been examined. Here, we showed the mRNA expression of mouse Zfta peaks on embryonic day (E) 17.5 in the wholemount of the lateral walls of the lateral ventricle. Zfta was expressed in the nuclei of FoxJ1-positive immature E1 (pre-E1) cells in E18.5 mouse embryonic brain. Interestingly, the transcription factors promoting ciliogenesis (ciliary TFs) (e.g., multicilin) and ZFTA-RELA upregulated luciferase activity using a 5 ' upstream sequence of ZFTA in cultured cells. Zfta(tm1/tm1) knock-in mice did not show developmental defects or abnormal fertility. In the Zfta(tm1/tm1) E1 cells, morphology, gene expression, ciliary beating frequency and ependymal flow were unaffected. These results suggest that Zfta is expressed in pre-E1 cells, possibly under the control of ciliary TFs, but is not essential for ependymal development or flow. This study sheds light on the mechanism of the ZFTA-RELA expression in the pathogenesis of ST-EPN-RELA: Ciliary TFs initiate ZFTA-RELA expression in pre-E1 cells, and ZFTA-RELA enhances its own expression using positive feedback.

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