{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:42:36Z","timestamp":1788910956145,"version":"build-2803163510"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30 DK074038"],"award-info":[{"award-number":["P30 DK074038"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2020,11]]},"abstract":"\n Significance Statement<\/jats:title>\n \n Nephrons are derived from nephron progenitor cells. Nephron progenitors are depleted during kidney development, which makes the kidney unable to regenerate nephrons. Therefore, understanding the signaling molecules that regulate nephron progenitor cell generation and maintenance is of great interest for kidney regeneration.\n Sprouty1<\/jats:italic>\n regulates nephron progenitor maintenance by inhibiting Fibroblast growth factor (FGF) signaling. Deletion of\n Sprouty1<\/jats:italic>\n rescues renal agenesis and nephron progenitor depletion in Fgf9\/20 loss-of-function kidneys. Deletion of one copy of\n Fgf8<\/jats:italic>\n further decreases FGF signaling, which blocks kidneys\u2019 response to\n Sprouty1<\/jats:italic>\n , resulting in failure of nephron progenitor maintenance. This study thus identifies the reciprocal functioning of FGF-Sprouty1 signaling during nephron progenitor development.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Spry1<\/jats:italic>\n ,\n Fgf9<\/jats:italic>\n , and\n Fgf20<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Loss of one copy of\n Spry1<\/jats:italic>\n counters effects of the loss of\n Fgf9<\/jats:italic>\n and\n Fgf20<\/jats:italic>\n , 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\n Fgf8<\/jats:italic>\n and\n Fgf20<\/jats:italic>\n results in kidney agenesis, defects in NPC proliferation, and cell death. Deleting one copy of\n Fgf8<\/jats:italic>\n reversed the effect of deleting one copy of\n Spry1<\/jats:italic>\n , which rescued the renal agenesis due to loss of\n Fgf9<\/jats:italic>\n and\n Fgf20<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2020040401","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T17:05:49Z","timestamp":1596560749000},"page":"2559-2572","source":"Crossref","is-referenced-by-count":25,"title":["Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction"],"prefix":"10.1681","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-1973","authenticated-orcid":false,"given":"Sung-Ho","family":"Huh","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska"},{"name":"Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, 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