Heartbeat regulates cardiogenesis by suppressing retinoic acid signaling via expression of miR-143

Mech Dev. Jan-Feb 2011;128(1-2):18-28. doi: 10.1016/j.mod.2010.09.002. Epub 2010 Sep 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Circulation / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Heart / embryology*
  • Heart / physiology*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oligonucleotides, Antisense / pharmacology
  • Organogenesis / drug effects
  • Organogenesis / genetics*
  • Phenotype
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Tretinoin / metabolism*
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • MIRN143 microRNA, zebrafish
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Zebrafish Proteins
  • Tretinoin
  • Aldh1a2 protein, zebrafish
  • Retinal Dehydrogenase