Fig. 1.

Molecular regulation of ureteric budding and branching morphogenesis. Eya1 (indirectly), Six1 and Pax2 (directly) activate transcription of GDNF, initializing budding and consequent branching of the ureter via Ret and Gfra1. In vitro studies have demonstrated a role of Dach1 as a co-repressor or co-activator of Six1, with Eya1 acting as a molecular switch. In vitro Bmp4 inhibits ectopic budding and branching of the ureter by inhibition of Gdnf signalling. In addition to its function in the Six-Dach-Eya network, Dach1 inhibits TGF-β/BMP4 signalling directly in human breast cancer cell lines (dashed line).