SOX18 is a target gene of the Shh-Ptc pathway in murine cerebellar granule cell precursors and is highly expressed in human desmoplastic medulloblastomas

Medulloblastomas (MBs) are the most frequent malignant brain tumours in childhood and can be subdivided into the classic and the desmoplastic variant. The latter arises from cerebellar granule cell progenitors (GCPs) of the external granule cell layer (EGL). Its pathogenesis is linked to an overactivation of the Sonic Hedgehog-Patched (Shh-Ptc) pathway. By culturing murine GCPs in the presence or absence of the morphogen Shh, respectively, we identified the gene for the transcription factor Sox18 to be highly induced by Shh using DNA microarray and subsequent competitive RT-PCR. In situ hybridization showed that sox18 is expressed in the EGL of the postnatally developing cerebellum. However, immunohistological studies on sox18 deficient mice did not hint to an essential role in cerebellar development. mRNA expression analysis in human MBs showed that SOX18 is highly expressed in the desmoplastic variant pointing to a potential role in the genesis of this MB subtype.