Congenital anomalies of the kidneys and urinary tract (CAKUT) are a common cause of kidney disease in infants as a result of defective embryonic development. To date only relatively few causative mutations were identified that account for a minority of CAKUT cases. Among the proteins encoded by the known disease-associated genes, transcription factors are considerably overrepresented. However, a comprehensive view of the transcriptional programs leading to renal progenitor determination and differentiation remains incomplete, thus limiting our ability to understand some of the developmental alterations leading to hereditary kidney anomalies. One aim of this project is to define and functionally analyze the core transcriptional regulatory programs that specify renal identity and guide the morphogenetic events of kidney morphogenesis. Using a systematic approach, involving analyses across different vertebrate species, we identify a core set of transcription factors with conserved expression during different stages of renal development. This set of factors will be functionally analyzed during lineage specification towards the cell types of the kidney. By overexpression and knockdown of candidate factors in Xenopus embryos and murine cell lines, we will establish a regulatory network of key transcription factors required for renal development. We will ask whether newly identified regulators of renal specification also constitute candidate loci for unmapped hereditary conditions of renal malformation in humans. Finally, we will use combinatorial expression of transcription factors to test their potential to direct murine and Xenopus cells towards renal fate in vitro.