Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

Abstract

The mature nephron forms from a simple epithelial vesicle into an elaborate structure with distinct regions of specialized physiological function. The molecular components driving the process of nephron development are not well understood. To identify genes that may be informative in this process we conducted a transcriptional profiling screen using Wnt4 mutant kidneys. In Wnt4-/- homozygous mice, condensates and pretubular aggregates are induced, however, epithelial renal vesicles fail to form and subsequent tubulogenesis is blocked. A transcriptional profile comparison between wildtype and Wnt4-/- mutant kidneys at E14.5 was performed using Affymetrix oligonucleotide microarrays to identify nephron-expressed genes. This approach identified 236 genes with expression levels >1.8-fold higher in wildtype versus mutant kidneys, amongst these were a number of known nephron component markers confirming the validity of the screen. These results were further detailed by wholemount in situ hybridization (WISH) of E15.5 urogenital systems (UGS). We annotated the spatial expression pattern of these genes into eight categories of expression. Genes expressed in renal vesicle and their derivatives, structures absent in the mutant, accounted for the largest number of the observed expression patterns. A number of additional genes in areas not directly overlapping the Wnt4 expression domain were also identified including the cap mesenchyme, the collecting duct, and the cortical interstitium. This study provides a useful compendium of molecular markers for the study of nephrogenesis. © 2008 Elsevier B.V. All rights reserved.