ZEB1 · The transcriptional network of the zinc-finger factor ZEB1 and its function in the embryonic nervous system and glioma development

Current interest in neural stem cells derives from the prospect of using them in brain repair strategies, but also to understand neurodevelopmental pathologies. This will require, however, a significant improvement of our understanding of the gene expression programs associated with their maintenance and differentiation, and how these are regulated. Recently, several lines of evidence suggest a regulatory function for the zinc-finger transcription factor ZEB1, both in embryonic neural stem/progenitor cells, and in human tumours of neural origin. Here we propose to use a multidisciplinary approach, combining mouse genetics and genomics, to characterize the function of ZEB1 in neural development. A thorough phenotypic analysis of ZEB1 loss-of-function mouse models will be performed, with a special focus on its role in neural progenitors. This will be complemented with the genome-wide characterization of its transcriptional network, using a combination of genomic location analysis with expression profiling. Moreover, a detailed comparison of the ZEB1 transcriptional programs in human foetal- and glioma-derived stem cells will be carried out, providing important insights into ZEB1 function in tumour initiation and development.