Wilms Tumor 1 (WT1) and Foxc2 are required for podocyte development in Xenopus

Abstract

Single‐gene knockout studies have shown that Foxc2, Lmx1b, MafB, Tcf21 and WT1 are the necessary transcriptional regulators of podocyte development. It is still unclear, however, whether these five transcription factors (TFs) can explain all aspects of podocyte development. To this end, we have used the Xenopus pronephros as a tool to study podocyte development.To test the roles of these five TFs in podocyte development, each was individually knocked down with antisense morpholino oligomer technology. In situ hybridization for podocyte TFs (Foxc2, Lmx1b, MafB, Tcf21 and WT1) and markers of terminal differentiation (Nephrin, Neph1, Glepp1 and Podocin) was used to analyze the resultant phenotype. These data were compiled to construct a gene regulatory network for podocyte development (PGRN). The PGRN displayed classical characteristics of a gene regulatory network, including master regulators, multi‐gene loops and a high degree of redundancy. Based on the network, we hypothesized that WT1 and Foxc2 are the master regulators of podocyte development. Simultaneous depletion of WT1 and Foxc2 resulted in loss of expression of downstream podocyte TFs (Lmx1b, MafB and Tcf21) and markers of terminal differentiation (Nephrin, Neph1, Glepp1 and Podocin); moreover, these embryos were characterized by a complete loss of the glomus structure. This work was supported by F30DK082121.Grant Funding SourceNIDDK