Nephron progenitor maintenance is controlled through fibroblast growth factors and sprouty1 interaction

Sung Ho Huh, Ligyeom Ha, Hee Seong Jang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background Nephron progenitor cells (NPCs) give rise to all segments of functional nephrons and are of great interest due to their potential as a source for novel treatment strategies for kidney disease. Fibroblast growth factor (FGF) signaling plays pivotal roles in generating and maintaining NPCs during kidney development, but little is known about the molecule(s) regulating FGF signaling during nephron development. Sprouty 1 (SPRY1) is an antagonist of receptor tyrosine kinases. Although SPRY1 antagonizes Ret-GDNF signaling, which modulates renal branching, its role in NPCs is not known. Methods Spry1, Fgf9, and Fgf20 compound mutant animals were used to evaluate kidney phenotypes in mice to understand whether SPRY1 modulates FGF signaling in NPCs and whether FGF8 functions with FGF9 and FGF20 in maintaining NPCs. Results Loss of one copy of Spry1 counters effects of the loss of Fgf9 and Fgf20, rescuing bilateral renal agenesis premature NPC differentiation, NPC proliferation, and cell death defects. In the absence of SPRY1, FGF9, and FGF20, another FGF ligand, FGF8, promotes nephrogenesis. Deleting both Fgf8 and Fgf20 results in kidney agenesis, defects in NPC proliferation, and cell death. Deleting one copy of Fgf8 reversed the effect of deleting one copy of Spry1, which rescued the renal agenesis due to loss of Fgf9 and Fgf20. Conclusions SPRY1 expressed in NPCs modulates the activity of FGF signaling and regulates NPC stemness. These findings indicate the importance of the balance between positive and negative signals during NPC maintenance.

Original languageEnglish (US)
Pages (from-to)2559-2572
Number of pages14
JournalJournal of the American Society of Nephrology
Volume31
Issue number11
DOIs
StatePublished - Nov 2020

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Nephron progenitor maintenance is controlled through fibroblast growth factors and sprouty1 interaction'. Together they form a unique fingerprint.

Cite this