During metanephric kidney development renin expression in the renal vasculature begins in larger vessels, shifting to smaller vessels and finally remaining restricted to the terminal portions of afferent arterioles at the entrance into the glomerular capillary network. The mechanisms determining the successive expression of renin along the vascular axis of the kidney are not well understood. Since the cAMP signaling cascade plays a central role in the regulation of both renin secretion and synthesis in the adult kidney, it seemed feasible that this pathway may also be critical for renin expression during kidney development. In the present study we determined the spatiotemporal development of renin expression and the development of the preglomerular arterial tree in mouse kidneys with renin-cell (RC) specific deletion of G_s, a core element for receptor activation of adenylyl cylases. We found that in the absence of the G_s protein renin expression was largely absent in the kidneys at any developmental stage, whereas the development of the preglomerular arterial tree was apparently normal. These data indicate that the maintenance of renin expression following a specific spatiotemporal pattern along the preglomerular vasculature critically depend of the availability of G_s. We infer from our data that the cAMP signaling pathway is not only critical for the regulation of renin synthesis and secretion in the mature kidney, but that it is also critical for establishing the juxtaglomerular expression site of renin during development.