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; Toshihiko Ogura

doi:10.1038/ncomms2978

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, Toshihiko Ogura

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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.

Original language	English
Article number	1978
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2978
Publication status	Published - 2013

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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title = "Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21",

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.",

author = "Toshihiro Banjo and Janin Grajcarek and Daisuke Yoshino and Hideto Osada and Miyasaka, {Kota Y.} and Kida, {Yasuyuki S.} and Yosuke Ueki and Kazuaki Nagayama and Koichi Kawakami and Takeo Matsumoto and Masaaki Sato and Toshihiko Ogura",

note = "Funding Information: We thank S. Takashima and A. Kawahara for supplying materials. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Science, Sports and Culture of Japan (to T.O.), and grants from the Takeda Science Foundation, the Naito Foundation and the Uehara Memorial Foundation (to T.O.). J.G. was supported by the Tohoku University Cooperative Laboratory Study Program (COLABS). T.B. was supported by Japan Society for the Promotion of Science.",

year = "2013",

doi = "10.1038/ncomms2978",

language = "English",

volume = "4",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21

AU - Banjo, Toshihiro

AU - Grajcarek, Janin

AU - Yoshino, Daisuke

AU - Osada, Hideto

AU - Miyasaka, Kota Y.

AU - Kida, Yasuyuki S.

AU - Ueki, Yosuke

AU - Nagayama, Kazuaki

AU - Kawakami, Koichi

AU - Matsumoto, Takeo

AU - Sato, Masaaki

AU - Ogura, Toshihiko

N1 - Funding Information: We thank S. Takashima and A. Kawahara for supplying materials. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Science, Sports and Culture of Japan (to T.O.), and grants from the Takeda Science Foundation, the Naito Foundation and the Uehara Memorial Foundation (to T.O.). J.G. was supported by the Tohoku University Cooperative Laboratory Study Program (COLABS). T.B. was supported by Japan Society for the Promotion of Science.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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