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.
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