Heartbeat regulates cardiogenesis by suppressing retinoic acid signaling via expression of miR-143.
Cardiogenesis proceeds with concomitant changes in hemodynamics to accommodate the circulatory demands of developing organs and tissues. In adults, circulatory adaptation is critical for the homeostatic regulation of blood circulation. In these hemodynamics-dependent processes of morphogenesis and adaptation, a mechanotransduction pathway, which converts mechanical stimuli into biological outputs, plays an essential role, although its molecular nature is largely unknown. Here, we report that expression of zebrafish miR-143 is dependent on heartbeat. Knocking-down miR-143 results in de-repression of retinoic acid signaling, and produces abnormalities in the outflow tracts and ventricles. Our data uncover a novel epigenetic link between heartbeat and cardiac development, with miR-143 as an essential component of the mechanotransduction cascade.
Miyasaka
Kota Y
KY
Graduate School of Life Sciences, Institute of Development, Aging and Cancer, Tohoku University, 4-1, Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
Kida
Yasuyuki S
YS
Banjo
Toshihiro
T
Ueki
Yosuke
Y
Nagayama
Kazuaki
K
Matsumoto
Takeo
T
Sato
Masaaki
M
Ogura
Toshihiko
T
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000196:embryology* / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014212:Tretinoin / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
C549612:MIRN143 microRNA, zebrafish; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; D014212:Tretinoin; C518907:Aldh1a2 protein, zebrafish; D050697:Retinal Dehydrogenase