In mammalian embryos, the metanephric kidney emerges from metanephric mesenchyme and ureteric bud epithelium, a process characterized by the synthesis of numerous new epithelial proteins and suppression of the activity of mesenchymal genes. I propose to study some of the many transcription factors which must be involved in directing this new gene actiVity. I have begun to approach this investigation by performing differential hybridization to find genes expressed in embryonic but not adult kidney and by screening an embryonic kidney cDNA library with probes for transcription factor motifs. One or two developmentally regulated candidate transcription factors will be studied by overexpression in cultured cells, by analyzing the promoter activity using luciferase reporter gene constructs, by investigation of transcriptional modulation through the use of chimeric transcription factor constructs, and identification of genes that are regulated by one of these transcription factor proteins. The study of transcription factors important in normal development of the kidney will improve our understanding of normal and disordered kidney growth and differentiation as well as neoplasia, and possibly recovery from acute renal injury. Knowledge gained from this work may help in the development of new therapies for acute renal failure and congenital kidney diseases.
| Whyte, D A; Li, C; Thomson, R B et al. (1999) Ksp-cadherin gene promoter. I. Characterization and renal epithelial cell-specific activity. Am J Physiol 277:F587-98 |
