Control of kidney development by calcium ions

From the formation of a simple kidney in amphibian larvae, the pronephros, to the formation of the more complex mammalian kidney, the metanephros, calcium is present through numerous steps of tubulogenesis and nephron induction. Several calcium-binding proteins such as regucalcin/SMP-30 and calbindin-D28k are commonly used to label pronephric tubules and metanephric ureteral epithelium, respectively. However, the involvement of calcium and calcium signalling at various stages of renal organogenesis was not clearly delineated. In recent years, several studies have pinpointed an unsuspected role of calcium in determination of the pronephric territory and for conversion of metanephric mesenchyme into nephrons. Influx of calcium and calcium transients have been recorded in the pool of renal progenitors to allow tubule formation, highlighting the occurrence of calcium-dependent signalling events during early kidney development. Characterization of nuclear calcium signalling is emerging. Implication of the non-canonical calcium/NFAT Wnt signalling pathway as an essential mechanism to promote nephrogenesis has recently been demonstrated. This review examines the current knowledge of the impact of calcium ions during embryonic development of the kidney. It focuses on Ca2+ binding proteins and Ca2+ sensors that are involved in renal organogenesis and briefly examines the link between calcium-dependent signals and polycystins.

► Calcium signalling is present throughout renal organogenesis.
► Calcium transients are required in renal progenitors to allow tubule formation.
► Calcineurin/NFAT signalling is involved in mesenchyme conversion into nephron.