Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells

Li Li, Katie B. Grausam, Jun Wang, Melody P. Lun, Jasmin Ohli, Hart G.W. Lidov, Monica L. Calicchio, Erliang Zeng, Jeffrey L. Salisbury, Robert J. Wechsler-Reya, Maria K. Lehtinen, Ulrich Schüller, Haotian Zhao

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Aberrant Notch signalling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly paediatric brain neoplasms. We developed animal models of CP tumours, by inducing sustained expression of Notch1, that recapitulate properties of human CP tumours with aberrant NOTCH signalling. Whole-transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumour cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate differentiation. A Shh-driven signalling cascade in the primary cilium occurs in tumour cells but not in epithelial cells. Lineage studies show that CP tumours arise from monociliated progenitors in the roof plate characterized by elevated Notch signalling. Abnormal SHH signalling and distinct ciliogenesis are detected in human CP tumours, suggesting the SHH pathway and cilia differentiation as potential therapeutic avenues.

Original languageEnglish (US)
Pages (from-to)418-430
Number of pages13
JournalNature Cell Biology
Issue number4
StatePublished - Mar 30 2016

ASJC Scopus subject areas

  • Cell Biology


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