Abstract
Fibroblast growth factor 23 (FGF23) is an endocrine hormone that is secreted by bone and acts on the kidney and parathyroid glands to regulate phosphate homeostasis. The effects of FGF23 on phosphate homeostasis are mediated by binding to FGF receptors and their coreceptor, αklotho, which are abundantly expressed in the kidney and parathyroid glands. However, the mechanisms of how FGF23 regulates phosphate handling in the proximal tubule are unclear because αklotho is primarily expressed in the distal nephron in humans and rodents. The purpose of this study was to gain additional insight into the FGF23-αklotho system by investigating the spatial and temporal aspects of the expression of fgf23 and αklotho in the zebrafish, Danio rerio. Here, we report that zebrafish fgf23 begins to be expressed after organogenesis and is continually expressed into adulthood in the corpuscles of Stannius, which are endocrine glands that lie in close proximity to the nephron and are thought to contribute to calcium and phosphate homeostasis in fish. Zebrafish αklotho expression can be detected by 24-h postfertilization in the brain, pancreas and the distal pronephros, and by 56-h postfertilization in liver. Expression in the distal pronephros persists throughout development, and by Day 5, there is also strong expression in the proximal pronephros. αklotho continues to be expressed in the tubules of the metanephros of the adult kidney. These data indicate conservation of the FGF23-αklotho system across species and suggest a likely role for αklotho in the proximal and distal tubules.