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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents



ID: 711920.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development
Authors:Carraro, G.; Shrestha, A.; Rostkovius, J.; Contreras, A.; Chao, C. M.; El Agha, E.; Mackenzie, B.; Dilai, S.; Guidolin, D.; Taketo, M. M.; Gunther, A.; Kumar, M. E.; Seeger, W.; De Langhe, S.; Barreto, G.; Bellusci, S.
Date of Publication (YYYY-MM-DD):2014-03
Title of Journal:Development
Volume:141
Issue / Number:6
Start Page:1272
End Page:1281
Audience:Not Specified
Abstract / Description:The regulation of the balance between proliferation and differentiation in the mesenchymal compartment of the lung is largely uncharacterized, unlike its epithelial counterpart. In this study, we determined that miR-142-3p contributes to the proper proliferation of mesenchymal progenitors by controlling the level of WNT signaling. miR-142-3p can physically bind to adenomatous polyposis coli mRNA, functioning to regulate its expression level. In miR-142-3p loss-of-function experiments, proliferation of parabronchial smooth muscle cell progenitors is significantly impaired, leading to premature differentiation. Activation of WNT signaling in the mesenchyme, or Apc loss of function, can both rescue miR-142-3p knockdown. These findings show that in the embryonic lung mesenchyme, the microRNA machinery modulates the level of WNT signaling, adding an extra layer of control in the feedback loop between FGFR2C and beta-catenin-mediated WNT signaling.
Free Keywords:Adenomatous Polyposis Coli Protein/metabolism; Animals; Cell Differentiation; Cell Proliferation; Female; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Genes, APC; Lung/cytology/*embryology/*metabolism; Mesenchymal Stromal Cells/*cytology/*metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs/antagonists & inhibitors/*genetics/*metabolism; Myocytes, Smooth Muscle/cytology/metabolism; Pregnancy; Receptor, Fibroblast Growth Factor, Type 2/metabolism; Wnt Signaling Pathway; beta Catenin/metabolism; Mesenchymal cell; WNT signaling; miRNA
External Publication Status:published
Document Type:Article
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:%^ 1435822045
Identifiers:ISSN:1477-9129 (Electronic) 0950-1991 (Linking) %R 10.1242/dev.105908
URL:http://www.ncbi.nlm.nih.gov/pubmed/24553287
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