Role of Asxl1 in kidney podocyte development via its interaction with Wtip.

Additional sex comb-like (ASXL) family proteins are chromatin factors that function in transcriptional activation and repression. However, the underlying mechanisms and biological implications have not been well established. Here, we identified a LIM domain-containing protein, Wilms tumor 1-interacting protein (WTIP), as an ASXL1-binding partner. Biochemical assays confirmed an interaction between the murine homologs Asxl1 and Wtip. The suppressive role of Wtip in WT1 function and the expression of Wtip in kidney podocytes prompted us to investigate the role of Asxl1 in the kidney using Asxl1-null mice. In homozygous Asxl1(-/-) embryos, defects in kidney size and glomerular podocyte morphology were observed. Furthermore, up-regulation of Wt1/Wtip target genes was observed in the kidneys of Asxl1-null embryos. Overall, these findings implicate Asxl1 in the maintenance of podocyte structure via its association with Wtip and in the regulation of WT1 signaling during early kidney development.

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