Forkhead box f1 is essential for migration of mesenchymal cells and directly induces integrin-beta3 expression

Dmitriy Malin, Il Man Kim, Evan Boetticher, Tanya V. Kalin, Sneha Ramakrishna, Lucille Meliton, Vladimir Ustiyan, Xiangdong Zhu, Vladimir V. Kalinichenko

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51 Scopus citations

Abstract

The Forkhead box f1 (Fox1) transcription factor is expressed in mesenchymal cells of the lung, liver, and gallbladder. Although Foxf1 deficiency causes severe abnormalities in the development of these organs, the molecular mechanisms underlying Foxf1 function remain uncharacterized. In this study we inactivated Foxf1 function in lung mesenchymal cells and mouse embryonic fibroblasts (MEFs) by use of either short interfering RNA duplexes or a membrane-transducing Foxf1 dominant negative (DN) mutant protein (Foxf1 DN), the latter of which is fused to the human immunodeficiency virus TAT protein transduction domain. Although Foxf1 did not influence DNA replication or cell survival, Foxf1 depletion severely diminished mesenchyme migration. Foxf1 deficiency in mesenchymal cells was associated with reduced expression of the integrin-beta3 (Itgβ3) subunit. Furthermore, we generated transgenic mice containing a tetracycline-inducible Foxf1 DN transgene. Adenovirus-mediated activation of Foxf1 DN in transgenic MEFs caused diminished cell migration and reduced Itgβ3 expression. A chromatin immunoprecipitation assay demonstrated that Foxf1 protein binds to the bp -871 to -815 region of the mouse Itgβ3 promoter. Deletion of the -871 to -815 Itgβ3 promoter region completely abolished the ability of Foxf1 to activate transcription of the Itgβ3 promoter in cotransfection experiments, indicating that the mouse Itgβ3 is a direct transcriptional target of Foxf1 protein. Foxf1 plays an essential role in mesenchyme migration by transcriptionally regulating Itgβ3.

Original languageEnglish (US)
Pages (from-to)2486-2498
Number of pages13
JournalMolecular and Cellular Biology
Volume27
Issue number7
DOIs
StatePublished - Apr 1 2007

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Malin, D., Kim, I. M., Boetticher, E., Kalin, T. V., Ramakrishna, S., Meliton, L., Ustiyan, V., Zhu, X., & Kalinichenko, V. V. (2007). Forkhead box f1 is essential for migration of mesenchymal cells and directly induces integrin-beta3 expression. Molecular and Cellular Biology, 27(7), 2486-2498. https://doi.org/10.1128/MCB.01736-06