The understanding of cellular growth and differentiation during kidney development offers promise for novel treatments of kidney disease and of prevention and is an area of considerable present excitement. This application proposes to identify zinc finger transcription factors whose expression may regulate early nephrogenesis. The focus will be on KZF- 1 (kidney zinc finger- 1), a novel zinc finger protein whose expression is modulated in nephrogenesis. Additionally, the application proposes to screen for other similar proteins from a kidney blastemal cell library.
The specific aims are: (1) To study the structure and function of KZF-1 by in situ hybridization and immunocytochemical analysis of its cellular expression during renal development, determination of a target DNA sequence to which KZF-1 binds, definition of domains important in nuclear localization, DNA binding, transactivation, and/or transrepression, and investigation of the role of KZF-1 in kidney differentiation in an organ culture model. (2) To identify novel zinc finger cDNAs from a blastemal cell library and screen for those whose expression is modulated in early nephrogenesis. Studies proposed in this application are likely to lead to a better molecular definition of nephrogenesis through a delineation of transcription factor cascades that control kidney growth and differentiation. The latter goal will ultimately be accomplished by identification of the regulators of these regulatory genes and by isolation of target genes whose expression these transcription factors control. Insights resulting from such work may have impact on the treatment of renal disease characterized by abnormal growth or development or those in which acute or chronic nephron injury occurs.
