Renin-synthesizing cells are known to be crucial in the regulation of blood pressure and fluid and electrolyte homeostasis. These cells have been considered as terminally differentiated because they synthesize a hormone (renin), are few in numbers, and are restricted to a juxtaglomerular localization in the adult mammalian kidney. However, recent work from our laboratory indicates that renin cells may be precursors for other cell types including but not limited to juxtaglomerular cells. It has also been accepted that renin cells derive from the mesoderm. We recently generated mice that express cre recombinase under the control of the renin locus and crossed them with reporter mice that after cre-mediated recombination express β-galactosidase or GFP in renin cells and its descendants even if renin expression subsequently ceases, therefore marking the cells' lineage (Developmental Cell 2004;6:719-28). We used these mice to explore the early evolution of renin cells in the embryo and to track their cellular contribution during organ development. We found that renin cells are already present in the developing ectoderm before organogenesis of the metanephric kidney has been initiated. Later during organogenesis, renin cells are found within multiple organs and tissues derived not only from the mesoderm (i.e kidney, adrenal gland, testis and bone marrow) but also from the endoderm (i.e. pancreas, gut, and trachea), ectoderm (i.e. skin) and neuroectoderm (i.e. choroid plexus and ependymal cells). Furthermore, the cells that expressed renin early during development differentiated into cells that persist throughout adult life. Altogether these experiments indicate that renin cells are more primitive than previously thought and act as precursor cells that differentiate into multiple cell types during organogenesis originally derived from all three layers of the early embryo and presumably act as a reservoir of cells ready to de-differentiate when injury and/or organ function is compromised.