Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development

Citations Over TimeTop 10% of 2010 papers

Abstract

The Wilms' tumor suppressor 1 (WT1) gene encodes a DNA- and RNA-binding protein that plays an essential role in nephron progenitor differentiation during renal development. To identify WT1 target genes that might regulate nephron progenitor differentiation in vivo, we performed chromatin immunoprecipitation (ChIP) coupled to mouse promoter microarray (ChIP-chip) using chromatin prepared from embryonic mouse kidney tissue. We identified 1663 genes bound by WT1, 86% of which contain a previously identified, conserved, high-affinity WT1 binding site. To investigate functional interactions between WT1 and candidate target genes in nephron progenitors, we used a novel, modified WT1 morpholino loss-of-function model in embryonic mouse kidney explants to knock down WT1 expression in nephron progenitors ex vivo. Low doses of WT1 morpholino resulted in reduced WT1 target gene expression specifically in nephron progenitors, whereas high doses of WT1 morpholino arrested kidney explant development and were associated with increased nephron progenitor cell apoptosis, reminiscent of the phenotype observed in Wt1(-/-) embryos. Collectively, our results provide a comprehensive description of endogenous WT1 target genes in nephron progenitor cells in vivo, as well as insights into the transcriptional signaling networks controlled by WT1 that might direct nephron progenitor fate during renal development.

Related Papers

• → Pax2 and Pax8 Regulate Branching Morphogenesis and Nephron Differentiation in the Developing Kidney(2007)220 cited
• → Principles of human and mouse nephron development(2022)59 cited
• → The Regulation of Apoptosis in Kidney Development: Implications for Nephron Number and Pattern?(2014)26 cited
• → Principles of Zebrafish Nephron Segment Development(2023)24 cited
• → Visualizing gene expression during zebrafish pronephros development and regeneration(2019)17 cited