During renal development renin expression shifts from large renal arteries towards smaller vessels in a defined spatiotemporal pattern, until it finally keeps restricted at the juxtaglomerular position at the terminal end of the afferent arterioles. The mechanisms determining the successive expression of renin along the vascular axis of the kidney are not well understood. In this context we have investigated the role of the cAMP signaling pathway, characterizing the spatiotemporal development of renin expression and the development of the preglomerular tree in mouse kidneys with renin cell specific deletion of Gsa-protein. We found that renin expression was largely absent in the kidneys of Gsa-deficient mice at any developmental stage as well as in adult kidneys. These data have shown that the maintenance of renin expression following a specific pattern along the preglomerular vascular tree essentially depends on the availability of Gsa and the cAMP signalling pathway is critical for the developmental shift of renin expression in the kidney. When limiting the factors, which trigger renin expression by the cAMP signaling pathway, we characterized the role of b- adrenergic receptors by investigating the spatiotemporal development of renin gene expression in mouse kidneys with deletion of b1 and b2 adrenergic receptors. We found that in the absence of both adrenergic receptors renin expression was markedly reduced at any developmental stage. Three-dimensional analyses showed lower renin expression in all segments of the vascular tree, whereas it was mostly absent in large renal arteries. These data indicate that the genetic disruption of b-adrenergic receptors come close to the renal phenotype, that results from switching off the stimulatory G-protein in the renin producing cells. We infer from our data that the sympathetic innervation via b-adrenergic receptors is critical for establishing the juxtaglomerular expression site of renin during renal development.