ArticleDevelopmental biology2015
Integrin β4 regulation of PTHrP underlies its contribution to mammary gland development.
Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Laminin Receptors in Peripheral Tissues: Functions Revealed by Analysis of Knockout Mice.The American journal of pathology · 2025Review
- Integration ATAC-Seq and RNA-Seq Analysis of Mammary Placodes in Erhualian and Bamaxiang Pigs Identified Candidate Genes Influencing Pig Teat Number Variation.Evolutionary applications · 2025Article
- Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker.Biomolecules · 2021Review
- The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.Nature communications · 2020Article
- Alveolar progenitor cells in the mammary gland are dependent on the β4 integrin.Developmental biology · 2020Article
- Deciphering the Mammary Stem Cell Niche: A Role for Laminin-Binding Integrins.Stem cell reports · 2019Article
- Synthetic hydrogels mimicking basement membrane matrices to promote cell-matrix interactions.Matrix biology : journal of the International Society for Matrix Biology · 2017Review
- Integrin alpha6 maintains the structural integrity of the kidney collecting system.Matrix biology : journal of the International Society for Matrix Biology · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The integrin α6β4 (referred to as β4) is expressed in epithelial cells where it functions as a laminin receptor. Although in vitro studies have implicated β4 in the biology of mammary epithelial cells, its contribution to mammary gland development has not been settled. To address this problem, we generated and analyzed itgb4(flox/flox)MMTV-Cre(-) and itgb4(flox/flox)MMTV-Cre(+) mice. The salient features of embryonic mammary tissue from itgb4(flox/flox)MMTV-Cre(+) mice were significantly smaller mammary buds and increased apoptosis in the surrounding mesenchyme. Also, compared to control glands, the itgb4-deleted mammary buds lacked expression of the progenitor cell marker CK14 and they were unable to generate mammary glands upon transplantation into cleared fat pads of recipient mice. Analysis of mammary glands at puberty and during pregnancy revealed that itgb4-diminished mammary tissue was unable to elongate and undergo branching morphogenesis. Micro-dissection of epithelial cells in the mammary bud and of the surrounding mesenchyme revealed that loss of β4 resulted in a significant decrease in the expression of parathyroid hormone related protein (PTHrP) in epithelial cells and of target genes of the PTHrP receptor in mesenchymal cells. Given that the phenotype of the itgb4-deleted mammary tissue mimicked that of the PTHrP knockout, we hypothesized that β4 contributes to mammary gland development by sustaining PTHrP expression and enabling PTHrP signaling. Indeed, the inability of itgb4-deleted mammary buds to elongate was rescued by exogenous PTHrP. These data implicate a critical role for the β4 integrin in mammary gland development and provide a mechanism for this role.
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