RRC ID 33674
Author Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka KY, Kida YS, Ueki Y, Nagayama K, Kawakami K, Matsumoto T, Sato M, Ogura T.
Title Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21.
Journal Nat Commun
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.
Volume 4
Pages 1978
Published 2013
DOI 10.1038/ncomms2978
PII ncomms2978
PMID 23748970
PMC PMC3709480
MeSH 3' Untranslated Regions / genetics Animals Base Sequence Blood Circulation / drug effects Blood Circulation / physiology* Butadienes / pharmacology Diacetyl / analogs & derivatives Diacetyl / pharmacology Gene Expression Regulation, Developmental / drug effects HEK293 Cells Heart Valves / embryology* Heart Valves / metabolism Hemodynamics* Humans MAP Kinase Signaling System / drug effects MicroRNAs / genetics* MicroRNAs / metabolism Molecular Sequence Data Morpholinos / pharmacology Nitriles / pharmacology Phenotype RNA, Messenger / genetics RNA, Messenger / metabolism Sequence Alignment Zebrafish / embryology* Zebrafish / genetics Zebrafish / physiology* Zebrafish Proteins / metabolism
IF 11.878
Times Cited 27
Zebrafish ko095/fli1:EGFP