Notch signaling promotes nephrogenesis by downregulating Six2

Eunah Chung, Patrick Deacon, Sierra Marable, Juhyun Shin, Joo Seop Park*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

During nephrogenesis, multipotent mesenchymal nephron progenitors develop into distinct epithelial segments. Each nephron segment has distinct cell types and physiological function. In the current model of kidney development,Notch signaling promotes the formation of proximal tubules and represses the formation of distal tubules. Here, we present a novel role of Notch in nephrogenesis. We show in mice that differentiation of nephron progenitors requires downregulation of Six2, a transcription factor required for progenitor maintenance, and that Notch signaling is necessary and sufficient for Six2 downregulation. Furthermore, we find that nephron progenitors lacking Notch signaling fail to differentiate into any nephron segments, not just proximal tubules. Our results demonstrate how cell fates of progenitors are regulated by a transcription factor governing progenitor status and by a differentiation signal in nephrogenesis.

Original languageEnglish (US)
Pages (from-to)3907-3913
Number of pages7
JournalDevelopment (Cambridge)
Volume143
Issue number21
DOIs
StatePublished - Nov 1 2016

Keywords

  • Kidney
  • Mouse
  • Nephrogenesis
  • Nephron progenitors
  • Nephron segmentation
  • Notch
  • Six2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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