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The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis.

Discovering the genetic and cellular mechanisms that drive cardiac morphogenesis remains a fundamental goal, as three-dimensional architecture greatly impacts functional capacity. During development, accurately contoured chambers balloon from a primitive tube in a process characterized by regional changes in myocardial cell size and shape. How these localized changes are achieved remains elusive. Here, we show in zebrafish that microRNA-143 (miR-143) is required for chamber morphogenesis through direct repression of adducin3 (add3), which encodes an F-actin capping protein. Knockdown of miR-143 or disruption of the miR-143-add3 interaction inhibits ventricular cardiomyocyte F-actin remodeling, which blocks their normal growth and elongation and leads to ventricular collapse and decreased contractility. Using mosaic analyses, we find that miR-143 and add3 act cell-autonomously to control F-actin dynamics and cell morphology. As proper chamber emergence relies on precise control of cytoskeletal polymerization, Add3 represents an attractive target to be fine-tuned by both uniform signals, such as miR-143, and undiscovered localized signals. Together, our data uncover the miR-143-add3 genetic pathway as essential for cardiac chamber formation and function through active adjustment of myocardial cell morphology.

Pubmed ID: 20460367


  • Deacon DC
  • Nevis KR
  • Cashman TJ
  • Zhou Y
  • Zhao L
  • Washko D
  • Guner-Ataman B
  • Burns CG
  • Burns CE


Development (Cambridge, England)

Publication Data

June 12, 2010

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK43351
  • Agency: NIDDK NIH HHS, Id: DK57521

Mesh Terms

  • 3' Untranslated Regions
  • Actins
  • Animals
  • Base Sequence
  • Calmodulin-Binding Proteins
  • Gene Expression Regulation, Developmental
  • Heart
  • In Situ Hybridization
  • MicroRNAs
  • Myocytes, Cardiac
  • Oligodeoxyribonucleotides, Antisense
  • Sequence Homology, Nucleic Acid
  • Zebrafish
  • Zebrafish Proteins