PURPOSE: Periostin is a secreted extracellular matrix protein that is differentially expressed in the developing kidney. We analyzed the temporal-spatial expression of periostin in the developing kidney and ureter as well as its roles in ureter branching morphogenesis, nephrogenesis and ureter development. MATERIALS AND METHODS: RNA in situ hybridization and immunofluorescence histochemistry were used to investigate the expression of periostin, αv integrin and α-smooth muscle actin during mouse renal and ureteral development. Metanephric explants were cultured in the presence of recombinant periostin, and ureteral branch points/tips and the glomerular number were quantified. Explants were also cultured in the presence of exogenous bone morphogenetic protein 4 and the effect on periostin mRNA levels was determined by quantitative real-time polymerase chain reaction. RESULTS: Periostin expression was observed in the mesenchyme surrounding the kidney and ureter, renal stroma, metanephric mesenchyme, ureter epithelium and developing nephrons. At embryonic day 15.5 periostin and αv integrin, a common subunit of periostin receptors, were co-expressed in smooth muscle cells of the ureter, renal artery and intrarenal arteries. Bone morphogenetic protein 4 up-regulated periostin mRNA expression and exogenous periostin inhibited branching morphogenesis and glomerular number. CONCLUSIONS: Bone morphogenetic protein 4 which inhibits ureteral branching morphogenesis and promotes smooth muscle cell migration in the ureter up-regulated periostin mRNA expression in the developing kidney. Ureteral smooth muscle cells express periostin and αv integrin. Periostin inhibited ureteral branching morphogenesis and glomerular number. Together these results suggest that periostin and bone morphogenetic protein 4 may have a role in branching morphogenesis, nephrogenesis and possibly smooth muscle cell migration.