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PLoS One. 2010 Apr 29;5(4):e10418. doi: 10.1371/journal.pone.0010418.

Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation--a mouse model for Cenani-Lenz syndrome.

Author information

1
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

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.

PMID:
20454682
PMCID:
PMC2861670
DOI:
10.1371/journal.pone.0010418
[Indexed for MEDLINE]
Free PMC Article

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