FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man.
The identity of niche signals necessary to maintain embryonic nephron progenitors is unclear. Here we provide evidence that Fgf20 and Fgf9, expressed in the niche, and Fgf9, secreted from the adjacent ureteric bud, are necessary and sufficient to maintain progenitor stemness. Reduction in the level of these redundant ligands in the mouse led to premature progenitor differentiation within the niche. Loss of FGF20 in humans, or of both ligands in mice, resulted in kidney agenesis. Sufficiency was shown in vitro where Fgf20 or Fgf9 (alone or together with Bmp7) maintained isolated metanephric mesenchyme or sorted nephron progenitors that remained competent to differentiate in response to Wnt signals after 5 or 2 days in culture, respectively. These findings identify a long-sought-after critical component of the nephron stem cell niche and hold promise for long-term culture and utilization of these progenitors in vitro.
Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St. Louis, MO 63110, USA.
Hila
H
Barak
Sung-Ho
SH
Huh
Shuang
S
Chen
Cécile
C
Jeanpierre
Jelena
J
Martinovic
Mélanie
M
Parisot
Christine
C
Bole-Feysot
Patrick
P
Nitschké
Rémi
R
Salomon
Corinne
C
Antignac
David M
DM
Ornitz
Raphael
R
Kopan
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology; D002454:Cell Differentiation; D000013:Congenital Abnormalities / Q000235:genetics; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000254:growth & development; D007674:Kidney Diseases / Q000151:congenital / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D009154:Mutation; D009399:Nephrons / Q000254:growth & development; D009924:Organ Culture Techniques; D055153:Stem Cell Niche / Q000502:physiology; D060449:Wnt Signaling Pathway
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C416003:FGF20 protein, human; C496459:FGF9 protein, human; C498812:Fgf20 protein, mouse; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; C525820:bmp7 protein, mouse; D005346:Fibroblast Growth Factors