YAP1/TAZ drives ependymoma-like tumour formation in mice

Noreen Eder, Federico Roncaroli, Marie-Charlotte Dolmart, Stuart Horswell, Felipe Andreiuolo, Helen R Flynn, Andre T Lopes, Suzanne Claxton, John-Paul Kilday, Lucy Collinson, Jun-Hao Mao, Torsten Pietsch, Barry Thompson, Ambrosius P Snijders, Sila K Ultanir

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2380
JournalNature Communications
Issue number1
Publication statusPublished - 13 May 2020


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