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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents



  history
ID: 648362.0, MPI für molekulare Biomedizin / Yearbook 2013
Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation
Authors:Sabine, A.; Agalarov, Y.; Maby-El Hajjami, H.; Jaquet, M.; Hagerling, R.; Pollmann, C.; Bebber, D.; Pfenniger, A.; Miura, N.; Dormond, O.; Calmes, J. M.; Adams, R. H.; Makinen, T.; Kiefer, F.; Kwak, B. R.; Petrova, T. V.
Date of Publication (YYYY-MM-DD):2012-02-14
Title of Journal:Dev Cell
Volume:22
Issue / Number:2
Start Page:430
End Page:445
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Lymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction.
Free Keywords:Animals; Blotting, Western; Calcineurin/genetics/*metabolism; Cell Proliferation; Connexins/genetics/*metabolism; Embryo, Mammalian/cytology/metabolism; Flow Cytometry; Forkhead Transcription Factors/*physiology; Gene Expression Regulation, Developmental; Homeodomain Proteins/*physiology; Lymphangiogenesis/*physiology; Lymphatic Vessels/*cytology/metabolism; Mechanotransduction, Cellular/*physiology; Mice; Mice, Knockout; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Signal Transduction; Tumor Suppressor Proteins/*physiology
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1878-1551 (Electronic) 1534-5807 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/22306086 [ID No:2]
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