Kidney Regeneration in Zebrafish Requires Wnt Signaling

The Wnt signaling pathway is critical to nephron regeneration in zebrafish, according to research presented by Caramei Kamei, PhD, at Kidney Week 2012. The zebrafish’s ability to restore skin, organs, and muscle without the use of stem cells has made it a model of interest for a wide range of potential therapeutic areas, including cardiovascular disease, retinopathy, and cancer. Identification of Wnt signaling involvement in kidney repair in zebrafish opens a pathway for new research into the understanding of kidney regeneration.“In contrast to mammalian kidneys, the zebrafish continuously adds new nephrons throughout its adult life,” said Kamei. Because zebrafish can repair and generate new nephrons from adult progenitor cells, she and her co-investigator Iain Drummond, PhD, of Massachusetts General Hospital wanted to determine what signaled the repair function to begin in the kidney.

An in situ hybridization study revealed that adult kidney progenitor cells and differentiating cell condensates that are used to regenerate nephrons were observed to express the Wnt receptor Frizzled-9b (FZD9B) and the Wnt target Lymphoid enhancer-binding factor 1 (LEF1). Colocalization of FZD9B and LHX1A-positive kidney progenitor cells also suggested Wnt signaling involvement in zebrafish nephrogenesis.

Induction of acute kidney injury using gentamicin increased the number of FZD9B-positive nephron progenitors; however, when Wnt signaling was blocked after injury, the number of progenitor cells declined. An increase in FZD9B expression with activation of Wnt signaling in the absence of injury further confirmed Wnt signaling’s role in kidney regeneration. “FZD9B is a new marker for newly forming nephrons as well as single cortical cells that are candidate kidney progenitor cells,” Kamei said. Because FZD9B is expressed in the human kidney, Wnt signaling may be a target of interest in further research.

December 2012 (Vol. 4, Number 12)