Ablation of β1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation

Matthew J. Naylor, Na Li, Julia Cheung, Emma T. Lowe, Elise Lambert, Rebecca Marlow, Pengbo Wang, Franziska Schatzmann, Timothy Wintermantel, Günther Schüetz, Alan R. Clarke, Ulrich Mueller, Nancy E. Hynes, Charles H. Streuli

    Research output: Contribution to journalArticlepeer-review


    Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of β1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of β1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured β1 integrin-null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. β1 integrin-null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where β1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for β1 integrins in prolactin signaling. This study demonstrates that β1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways. © The Rockefeller University Press.
    Original languageEnglish
    Pages (from-to)717-728
    Number of pages11
    JournalJournal of Cell Biology
    Issue number4
    Publication statusPublished - 21 Nov 2005


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