Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but highly restricted, specialised endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extra-renal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation, but was modulated by inhibition of angiotensin converting enzyme and altered salinity. Our data in larval fish is consistent with conservation of renin's physiologic functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signalling and endothelium are essential for developmental renin expression. Following inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are amongst the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions.
- Copyright © 2015, American Journal of Physiology - Renal Physiology