Localisation of the SRY-related HMG box protein, SOX9, in rodent brain.

Human mutations in the transcription factor gene, SOX9, cause campomelic dysplasia (CD), a severe dwarfism associated with brain abnormalities including dilation of lateral ventricles, hypoplasia of the corpus callosum and cerebellum defects. To improve our understanding of how SOX9 contributes to the molecular genetic pathway of brain development we sought to investigate the distribution of SOX9 protein in rat and mouse brain. The regions of SOX9 expression identified in this study correlated with the sites of reported brain abnormalities in CD patients. SOX9 immunoreactivity was observed in nuclei of scattered cells throughout the brain, in the ependymal layer and cells of the choroid plexus. In the forebrain most SOX9-immunoreactive nuclei co-localised with the glial astrocyte marker S-100. In the cerebellum, SOX9 was observed mostly in cells surrounding Purkinje cells, which were identified, by electron microscopy, as Golgi epithelial cells, also known as Bergmann glia. Using SOX9 antibody as a marker for the precursors of Bergmann glia, we traced their origin during mouse development. At embryonic day (E)14.5 and E16.5, SOX9 immunoreactivity was present mainly in the primordial choroid plexus, and ventricular zone. By E18.5, SOX9 was observed in the granular cell and Purkinje cell layers but no labelling was detectable in the external granular layer. These results suggest that SOX9 immunoreactivity is a marker for Bergmann cells during development and favour the proposed origin of the secondary glial scaffold arising from Bergmann cells derived exclusively from the ventricular zone.