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PMID: 19503830 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development.

PloS one ·Vol. 4 ·No. 6 ·2009-06-05 ·Pages e5813

Lindvall C, Zylstra CR, Evans N, West RA, Dykema K, Furge KA, Williams BO

Abstract

Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such signals play central roles during development and in disease. We have previously shown that Lrp5 is required for ductal stem cell activity and that loss of Lrp5 delays normal mammary development and Wnt1-induced tumorigenesis. Here we show that canonical Wnt signals through the Lrp6 co-receptor are also required for normal mouse mammary gland development. Loss of Lrp6 compromises Wnt/beta-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis. Heterozygosity for an inactivating mutation in Lrp6 is associated with a reduced number of terminal end buds and branches during postnatal development. While Lrp6 is expressed in both the basal and luminal mammary epithelium during embryogenesis, Lrp6 expression later becomes restricted to cells residing in the basal epithelial layer. Interestingly, these cells also express mammary stem cell markers. In humans, increased Lrp6 expression is associated with basal-like breast cancer. Taken together, our results suggest both overlapping and specific functions for Lrp5 and Lrp6 in the mammary gland.

MeSH Terms
Animals Cell Separation Female Flow Cytometry Gene Expression Profiling Gene Expression Regulation, Developmental Haplotypes LDL-Receptor Related Proteins/metabolism,physiology Low Density Lipoprotein Receptor-Related Protein-5 Low Density Lipoprotein Receptor-Related Protein-6 Mammary Glands, Animal/metabolism,physiology Mice Mice, Inbred C57BL Mice, Transgenic Signal Transduction Wnt Proteins/metabolism
Chemicals
LDL-Receptor Related Proteins LRP5 protein, human LRP6 protein, human Low Density Lipoprotein Receptor-Related Protein-5 Low Density Lipoprotein Receptor-Related Protein-6 Lrp5 protein, mouse Lrp6 protein, mouse Wnt Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lindvall Charlotta
Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan, United States of America. [email protected]
Zylstra Cassandra R
Evans Nicole
West Richard A
Dykema Karl
Furge Kyle A
Williams Bart O
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0005813
Email
[email protected]
Published
2009-06-05
Epub
2009-00-05
Pages
e5813
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2686096
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0005813 PMC Full Text View journal details
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