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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2012-arch     Display Documents

ID: 645177.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2012-arch
Mechanoinduction of lymph vessel expansion.
Authors:Planas-Paz, Lara; Strilić, Boris; Goedecke, Axel; Breier, Georg; Fässler, Reinhard; Lammert, Eckhard
Date of Publication (YYYY-MM-DD):2012
Title of Journal:The EMBO Journal
Issue / Number:4
Start Page:788
End Page:804
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:In the mammalian embryo, few mechanical signals have been identified to influence organ development and function. Here, we report that an increase in the volume of interstitial or extracellular fluid mechanically induces growth of an organ system, that is, the lymphatic vasculature. We first demonstrate that lymph vessel expansion in the developing mouse embryo correlates with a peak in interstitial fluid pressure and lymphatic endothelial cell (LEC) elongation. In 'loss-of-fluid' experiments, we then show that aspiration of interstitial fluid reduces the length of LECs, decreases tyrosine phosphorylation of vascular endothelial growth factor receptor-3 (VEGFR3), and inhibits LEC proliferation. Conversely, in 'gain-of-fluid' experiments, increasing the amount of interstitial fluid elongates the LECs, and increases both VEGFR3 phosphorylation and LEC proliferation. Finally, we provide genetic evidence that β1 integrins are required for the proliferative response of LECs to both fluid accumulation and cell stretching and, therefore, are necessary for lymphatic vessel expansion and fluid drainage. Thus, we propose a new and physiologically relevant mode of VEGFR3 activation, which is based on mechanotransduction and is essential for normal development and fluid homeostasis in a mammalian embryo.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:nn
Affiliations:MPI für molekulare Zellbiologie und Genetik
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