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Abstract: FR-PO750

Fibroblast Growth Factor Signaling Mediates Progenitor Cell Aggregation and Nephron Regeneration in the Adult Zebrafish Kidney

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

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

The zebrafish kidney regenerates after injury by development of new nephrons from resident adult kidney stem cells. Although adult kidney progenitor cells have been characterized by transplantation and single cell RNA seq, signals that stimulate new nephron formation are not known.

Methods

Adult wild type and Tg(lhx1a:EGFP) and Tg(hsp70:dn-fgfr1) transgenic zebrafish kidneys were injured by gentamicin injection. Regeneration was observed by in situ hybridization, immunofluorescence, and qPCR analyses.

Results

We demonstrate that fibroblast growth factors and FGF signaling is rapidly induced after kidney injury and that FGF signaling is required for recruitment of progenitor cells to sites of new nephron formation. Chemical or dominant negative blockade of Fgfr1 prevented formation of nephron progenitor cell aggregates after injury and during kidney development. Implantation of FGF soaked beads induced local aggregation of lhx1a:EGFP+ kidney progenitor cells.

Conclusion

Our results reveal a previously unexplored role for FGF signaling in recruitment of renal progenitors to sites of new nephron formation and suggest a role for FGF signaling in maintaining cell adhesion and cell polarity in newly forming kidney epithelia.

Funding

  • NIDDK Support