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Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation

Sabine, Amélie
Agalarov, Yan
Maby-El Hajjami, Hélène
Jaquet, Muriel
Hägerling, René
Pollmann, Cathrin
Bebber, Damien
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Published in Developmental Cell. 2012, vol. 22, no. 2, p. 430-45
Abstract 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.
Keywords AnimalsBlotting, WesternCalcineurin/genetics/metabolismCell ProliferationConnexins/genetics/metabolismEmbryo, Mammalian/cytology/metabolismFlow CytometryForkhead Transcription Factors/physiologyGene Expression Regulation, DevelopmentalHomeodomain Proteins/physiologyLymphangiogenesis/physiologyLymphatic Vessels/cytology/metabolismMechanotransduction, Cellular/physiologyMiceMice, KnockoutRNA, Messenger/geneticsReal-Time Polymerase Chain ReactionSignal TransductionTumor Suppressor Proteins/physiology
PMID: 22306086
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Research group L'athérosclérose (665)
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SABINE, Amélie et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. In: Developmental Cell, 2012, vol. 22, n° 2, p. 430-45. doi: 10.1016/j.devcel.2011.12.020 https://archive-ouverte.unige.ch/unige:26723

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Deposited on : 2013-03-12

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