YAP1/TAZ drives ependymoma-like tumour formation in mice
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Noreen Eder Federico Roncaroli Marie-Charlotte Dolmart Stuart Horswell Felipe Andreiuolo Helen Flynn Andre Teixeira Lopes Suzanne Claxton John-Paul Kilday Lucy Collinson Jun-Hao Mao Torsten Pietsch Barry Thompson Bram Snijders Sila UltanirAbstract
YAP1 gene fusions have been observed in a subset of paediatric ependymomas. Here we show that, ectopic expression of active nuclear YAP1 (nlsYAP5SA) in ventricular zone neural progenitor cells using conditionally-induced NEX/NeuroD6-Cre is sufficient to drive brain tumour formation in mice. Neuronal differentiation is inhibited in the hippocampus. Deletion of YAP1's negative regulators LATS1 and LATS2 kinases in NEX-Cre lineage in double conditional knockout mice also generates similar tumours, which are rescued by deletion of YAP1 and its paralog TAZ. YAP1/TAZ-induced mouse tumours display molecular and ultrastructural characteristics of human ependymoma. RNA sequencing and quantitative proteomics of mouse tumours demonstrate similarities to YAP1-fusion induced supratentorial ependymoma. Finally, we find that transcriptional cofactor HOPX is upregulated in mouse models and in human YAP1-fusion induced ependymoma, supporting their similarity. Our results show that uncontrolled YAP1/TAZ activity in neuronal precursor cells leads to ependymoma-like tumours in mice.
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Journal Nature Communications
Volume 11
Issue number 1
Pages 2380
Available online
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Publisher website (DOI) 10.1038/s41467-020-16167-y
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Europe PubMed Central 32404936
Pubmed 32404936
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