Kidney Regeneration in Fish

Chronic and acute kidney injury damages nephrons, the blood filtering tubules in the kidney. Although mammalian kidneys can regenerate the tubular epithelium of the nephron, no new nephrons are made during adulthood. In contrast, fish are capable of growing nephrons de novo throughout their life. A better understanding of this 'neo-nephrogenic' response in fish may lead to the development of novel regenerative therapies to treat kidney disease in humans.In this review, nephron formation in the fish mesonephric kidney during normal growth and in response to acute injury is examined at the morphological and molecular levels. Included is an overview of the recent discovery of migratory nephron progenitors that, following transplantation, can engraft host kidneys and give rise to functional nephrons.Mesonephric nephron progenitors appear during the larval stage, migrate together to form clusters, activate the expression of conserved nephrogenic genes, and epithelialize into nascent nephrons in a process that resembles mammalian nephron formation. Nephron progenitors persist in the adult fish kidney and continue to add new nephrons at a basal rate as the fish grows in size. Following acute kidney injury, nephron formation is significantly increased, allowing the fish to rapidly regenerate lost nephrons. Transplantation of nephron progenitors into the kidney results in the formation of donor-derived nephrons in the recipient fish.