The Sox family of transcription factors are versatile regulators of stem and progenitor cell fate. Sox2 is a well-characterized member of this family and plays essential roles during animal development and in adult stem cells. Accumulating evidence suggests that dysregulation of Sox2 expression is involved in key steps during tumorigenesis. However, the underlying molecular mechanisms of Sox2 in tumor formation and the Sox2 target genes mediating these phenotypes remain elusive.Here, using mouse skin as a model tissue, I propose to systematically profile the Sox2 regulatory network by RNA seq and ribosomal profiling. To determine the physiological relevance of Sox2 target gene changes, I plan to carry out an shRNA screen to uncover novel mediator of Sox2-dependent tissue growth. I will take advantage of the ultrasound-guided in utero microinjections of lentivirus into the amniotic cavity, which has been recently developed in our lab and allows to test the function of thousands of genes simultaneously. I will confirm and document the role of novel targets in mouse and human squamous cell carcinomas. Understanding how this stem cell regulator controls these key steps during tumor progression could be exploited not only for cancer diagnostics, but also in designing novel cancer therapies.