Sine oculis homolog 1 (SIX1) is expressed in metanephric mesenchyme and the expression is enhanced by Eyes absent homolog 1 (EYA1) (inferred from mouse homologs). The metanephric mesenchyme interacts with the nephric duct to regulate formation of the ureteric bud. Expression of SIX1 continues into development of nephrons where it is regulated by either SIX1 or SIX2 (O'Brien et al. 2016). In mice lacking Eya1, expression of Six1 is reduced but not absent (Xu et al. 1999). In mice lacking Six1, the metanephric mesenchyme is incapable of forming tubules even when induced by signals from wild-type tissue (Xu et al. 2003).