Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation - a mouse model for cenani-lenz syndrome

Courtney M. Karner, Martin F. Dietrich, Eric B. Johnson, Natalie Kappesser, Christian Tennert, Ferda Percin, Bernd Wollnik, Thomas J. Carroll, Joachim Herz

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Background: Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. Methods and Principal Findings: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. Conclusion: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4-/- mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidney malformations in humans and mice.

Original languageEnglish (US)
Article numbere10418
JournalPloS one
Volume5
Issue number4
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation - a mouse model for cenani-lenz syndrome'. Together they form a unique fingerprint.

  • Cite this