論文

査読有り
2010年5月

Notch2 Activation in the Embryonic Kidney Depletes Nephron Progenitors

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
  • Sayoko Fujimura
  • ,
  • Qing Jiang
  • ,
  • Chiyoko Kobayashi
  • ,
  • Ryuichi Nishinakamura

21
5
開始ページ
803
終了ページ
810
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1681/ASN.2009040353
出版者・発行元
AMER SOC NEPHROLOGY

Successive activation of Wnt4 and Notch2 generates nephrons from the metanephric mesenchyme. Mesenchymal-to-epithelial transition requires Wnt4, and normal development of the proximal nephron (epithelia of glomeruli and proximal tubules) requires Notch2. It is unknown, however, whether Notch2 dictates the fate of the proximal nephron directly. Here, we generated a mutant strain of mice with activated Notch2 in Six2-containing nephron progenitor cells of the metanephric mesenchyme. Notch2 activation did not skew the cell fate toward the proximal nephron but resulted in severe kidney dysgenesis and depletion of Six2-positive progenitors. We observed ectopic expression of Wnt4 and premature tubule formation, similar to the phenotype of Six2-deficient mice. Activation of Notch2 in the progenitor cells suppressed Pax2, an upstream regulator of Six2, possibly through Hesr genes. Taken together, these data suggest that a positive feedback loop exists between Notch2 and Wnt4, and that Notch2 stabilizes, rather than dictates, nephron fate by shutting down the maintenance of undifferentiated progenitor cells, thereby depleting this population.

Web of Science ® 被引用回数 : 43

リンク情報
DOI
https://doi.org/10.1681/ASN.2009040353
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000277600400015&DestApp=WOS_CPL