The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis.

摘要: Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis govern differentiation tumour. Knock-out Irx3−/Irx5− mice showed strongly reduced embryonic nephron formation. In human foetal tumour, expression was already activated in early proliferative blastema, whereas protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model IRX3−/− cells formed bulky renal tumours dominated by immature mesenchyme active canonical WNT/β-catenin-signalling. contrast, IRX5−/− displayed activation Hippo non-canonical WNT-signalling generated small abundant tubulogenesis. Our findings suggest promotion signalling or inhibition could be route towards therapy which WNT5A candidate molecule enforced maturation. (Less)