header logo image header logo text
Downloads Login
Research
General Information
ZIRC
ZFIN ID: ZDB-PUB-100518-4
The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis
Deacon, D.C., Nevis, K.R., Cashman, T.J., Zhou, Y., Zhao, L., Washko, D., Guner-Ataman, B., Burns, C.G., and Burns, C.E.
Date: 2010
Source: Development (Cambridge, England) 137(11): 1887-1896 (Journal)
Registered Authors: Burns (Erter), Caroline, Burns, Geoff, Cashman, Tim, Deacon, Dekker, Zhao, Long, Zhou, Yong
Keywords: microRNA, miR-143(mir143), Adducin, Zebrafish, Heart development, Organogenesis
MeSH Terms:
  • 3' Untranslated Regions
  • Actins/metabolism
  • Animals
  • Base Sequence
  • Calmodulin-Binding Proteins/genetics*
  • Calmodulin-Binding Proteins/physiology
  • Gene Expression Regulation, Developmental
  • Heart/embryology*
  • In Situ Hybridization
  • MicroRNAs/genetics*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/physiology
  • Oligodeoxyribonucleotides, Antisense/genetics
  • Sequence Homology, Nucleic Acid
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology
PubMed: 20460367 Full text @ Development
FIGURES
ABSTRACT
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.
ADDITIONAL INFORMATION