Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis

Pei Wang, Fred A. Pereira, Duane Beasley, Hui Zheng

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Mammalian presenilins consist of two highly homologous proteins, PSEN1 and PSEN2, which share redundant activities in Notch processing and signaling. To bypass the early lethality of the Psen1- and Psen2-double (PSEN) null embryos, we used a human PSEN1 transgene to rescue the somite patterning defects in PSEN-null animals and to allow a determination of the function of presenilins in late embryogenesis. We report here that expression of the human PSEN1 transgene supported the survival of PSEN-null embryos to the perinatal stage. However, presenilin deficiency in the kidney led to severe nephrogenesis defects and virtually no comma- or S-shaped bodies, or mature glomeruli were formed. We document that the mesenchyme was induced which could further progress to renal vesicles in the PSEN-null kidney, indicating that the presenilins are not essential for the inductive interactions and mesenchyme to epithelium transition. However, renal vesicles failed to pattern to form proximal tubules and glomerular epithelium. A presenilin-dependent, signaling-competent form of Notch1 was detected in mesenchymal derivatives but not in the ureteric buds of wild-type mice. Consistent with an obligatory role of presenilins in Notch processing and activation, the active form of Notch1 and its downstream target Hesr1 were absent in the PSEN-null kidney. Importantly, sustained Notch1 signaling was required for the maintenance of Notch ligand Jag1 expression. These results identify presenilins as one determinant of renal vesicle patterning in the developing mouse kidney, and we hypothesize that they act through the Notch signaling pathway.

Original languageEnglish (US)
Pages (from-to)5019-5029
Number of pages11
JournalDevelopment
Volume130
Issue number20
DOIs
StatePublished - Oct 1 2003

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Keywords

  • Kidney
  • Nephrogenesis
  • Notch
  • Patterning
  • Presenilin
  • Proximal tubule

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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