Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21

Toshihiro Banjo, Janin Grajcarek, Daisuke Yoshino, Hideto Osada, Kota Y. Miyasaka, Yasuyuki S. Kida, Yosuke Ueki, Kazuaki Nagayama, Koichi Kawakami, Takeo Matsumoto, Masaaki Sato and Toshihiko Ogura ()
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Toshihiro Banjo: Graduate School of Life Sciences, Tohoku University
Janin Grajcarek: Graduate School of Life Sciences, Tohoku University
Daisuke Yoshino: Biological Nanoscale Reactive Flow Laboratory, Institute of Fluid Science, Tohoku University
Hideto Osada: Graduate School of Life Sciences, Tohoku University
Kota Y. Miyasaka: Graduate School of Life Sciences, Tohoku University
Yasuyuki S. Kida: Mesenchymal Stem Cell Dynamics Research Team, Research Center for Stem Cell Engineering, National Institutes of Advanced Industrial Science and Technology
Yosuke Ueki: Graduate School of Biomedical Engineering, Tohoku University
Kazuaki Nagayama: Nagoya Institute of Technology, Gokisho, Showa, Nagoya, Aichi 466-8555, Japan
Koichi Kawakami: National Institute of Genetics
Takeo Matsumoto: Nagoya Institute of Technology, Gokisho, Showa, Nagoya, Aichi 466-8555, Japan
Masaaki Sato: Graduate School of Biomedical Engineering, Tohoku University
Toshihiko Ogura: Graduate School of Life Sciences, Tohoku University

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Heartbeat is required for normal development of the heart, and perturbation of intracardiac flow leads to morphological defects resembling congenital heart diseases. These observations implicate intracardiac haemodynamics in cardiogenesis, but the signalling cascades connecting physical forces, gene expression and morphogenesis are largely unknown. Here we use a zebrafish model to show that the microRNA, miR-21, is crucial for regulation of heart valve formation. Expression of miR-21 is rapidly switched on and off by blood flow. Vasoconstriction and increasing shear stress induce ectopic expression of miR-21 in the head vasculature and heart. Flow-dependent expression of mir-21 governs valvulogenesis by regulating the expression of the same targets as mouse/human miR-21 (sprouty, pdcd4, ptenb) and induces cell proliferation in the valve-forming endocardium at constrictions in the heart tube where shear stress is highest. We conclude that miR-21 is a central component of a flow-controlled mechanotransduction system in a physicogenetic regulatory loop.

Date: 2013
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DOI: 10.1038/ncomms2978

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