Caspase activity is required for nephrogenesis in the developing mouse metanephros.

Programmed cell death is a mechanism through which organisms get rid of unwanted cells and is thought to be an important process in organogenesis. Although large-scale cell death is observed in the developing kidney, the precise roles of cell death in kidney organogenesis remain to be elucidated. To address this question, we prevented cell death in metanephric explants by applying caspase inhibitors. Administration of caspase inhibitors (Z-D-CH2DCB and Ac-DEVD-CHO) effectively prevented the cell death that is normally observed in nondifferentiating mesenchymal cells. Both ureteric bud branching and nephrogenesis were prevented by caspase inhibition. Our results suggest that caspases are crucial in kidney organogenesis and cell death in the nondifferentiating mesenchyme. Copyright 1999 Academic Press.