Abstract: FR-PO252

FGFs Are Required for Stem Cell Recruitment to Nephrogenic Aggregates during Adult Zebrafish Kidney Regeneration

Session Information

  • Stem Cells
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 402 Stem Cells

Authors

  • Gallegos, Thomas F., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Kamei, Caramai Nanae, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Drummond, Iain A., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

In zebrafish, adult kidney injury (AKI) results in stem cell-mediated regeneration by the de novo production of new nephrons. This process occurs by progenitor cell aggregation and differentiation on kidney collecting ducts, leading to the insertion of new nephrons. Expression of dusp6, a transcriptional readout of FGF signaling, was induced upon AKI, suggesting a role for FGF signaling in new nephron formation. Early broad dusp6 expression became restricted to single cells and ultimately to nephrogenic aggregates abutting mature collecting ducts. In addition to dusp6, nascent nephrons are marked by expression of lhx1a. After gentamicin-induced AKI, pharmacological or dominant-negative based genetic inhibition of FGFR signaling completely prevented recruitment of progenitor cells to dusp6 and lhx1a-expressing nephrogenic aggregates. In juvenile Tg(lhx1a:egfp) zebrafish treated with FGFR inhibitor during developmental nephrogenesis, progenitor cells survive but fail to condense into organized aggregates. Upon kidney injury, expression of fgf4, fgf8a, fgf10a, and the receptors fgfr1 and fgfr4 were induced, suggesting multiple roles for FGF signaling in the formation of nephrogenic aggregates from single cell progenitors. By qPCR of fractionated kidneys, fgf4 and fgf10a were found to be specifically expressed in the tubular fraction of the injured kidney, suggesting that these ligands may play a role in recruiting nephrogenic cells to injured tubules. fgf8a expression was restricted to the most distal end of the nephrogenic aggregate, suggesting a role in patterning the new nephron aggregate. Our results demonstrate essential roles for FGF in recruitment of progenitor cells and patterning of nephrogenic aggregates during kidney regeneration in the adult zebrafish.

Funding

  • NIDDK Support