ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO749

Sprouty1 Regulates FGF Signaling-Mediated Nephron Progenitor Maintenance

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Author

  • Huh, Sung-Ho, University of Nebraska Medical Center , Omaha, Nebraska, United States
Background

Nephron progenitors maintain and differentiate with various signaling cascades. FGF9 and FGF20 play pivotal roles in generating and maintaining nephron progenitors during kidney development. However, molecules regulating FGF signaling during nephron progenitor development is not known. Sprouty (Spry) is an antagonist of receptor tyrosine kinases. In developing kidney, Spry1 is expressed in the ureteric buds and regulates Ret-GDNF-dependent renal branch morphogenesis. Although Spry1 also expressed in the nephron progenitors, function of Spry1 in this population is still elusive.

Methods

To understand whether Spry1 antagonize function of FGF9/20 induced nephron progenitors, we generated Spry1, Fgf9, Fgf20 triple mutant animals and evaluated kidney phenotypes.

Results

Deletion of Spry1 rescues bilateral renal agenesis caused by deletion of both Fgf9 and Fgf20. In addition, deletion of Spry1 normalizes number of nephron progenitors in Fgf9 and Fgf20 hypomorphic kidneys. Nephron progenitor specific deletion of Spry1 also rescues loss of Fgf9 and Fgf20 induced bilateral renal agenesis. Further genetic analyses identified Fgf8 compensates loss of Fgf9 and Fgf20 at the background of Spry1 mutant.

Conclusion

This data demonstrate that Spry1 expressed in nephron progenitors antagonize FGF signaling to balance nephron progenitor maintenance.

Funding

  • NIDDK Support