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ZFIN ID: ZDB-PUB-120724-8
Progesterone and AdipoQ Receptor 11 Links Ras Signaling to Cardiac Development in Zebrafish
Huang, H., Jin, T., He, J., Ding, Q., Xu, D., Wang, L., Zhang, Y., Pan, Y., Wang, Z., and Chen, Y.
Date: 2012
Source: Arterioscler. Thromb. Vasc. Biol. 32(9): 2158-2170 (Journal)
Registered Authors:
Keywords: heart development, heart morphogenesis, Ras, subcellular organelle, zebrafish
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation
  • Cell Shape
  • Cloning, Molecular
  • Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Genotype
  • Golgi Apparatus/metabolism
  • Heart/drug effects
  • Heart/embryology*
  • Heart Defects, Congenital/embryology
  • Heart Defects, Congenital/genetics
  • Heart Defects, Congenital/metabolism
  • Luminescent Proteins/biosynthesis
  • Luminescent Proteins/genetics
  • Molecular Sequence Data
  • Morphogenesis
  • Morpholinos/administration & dosage
  • Myocytes, Cardiac/drug effects
  • Myocytes, Cardiac/metabolism*
  • Myocytes, Cardiac/pathology
  • Phenotype
  • Protein Kinase Inhibitors/pharmacology
  • Receptors, Adiponectin/genetics
  • Receptors, Adiponectin/metabolism*
  • Receptors, Progesterone/genetics
  • Receptors, Progesterone/metabolism*
  • Signal Transduction*/drug effects
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • ras Proteins/genetics
  • ras Proteins/metabolism*
PubMed: 22814753 Full text @ Arterioscler. Thromb. Vasc. Biol.

Objective—Progesterone and adipoQ receptor (PAQR) 10 and PAQR11 are 2 highly homologous genes involved in compartmentalized Ras signaling in the Golgi apparatus. The aim of this study was to investigate the physiological functions of PAQR10 and PAQR11.

Methods and Results—We used zebrafish as a model system to analyze the potential function of PAQR10/PAQR11. The expression profiles of PAQR10 and PAQR11 in zebrafish embryos are overlapping in many areas, but only PAQR11 is expressed in the developing heart. Knockdown of PAQR11 but not PAQR10 in zebrafish embryos causes cardiac developmental defects, including dilation of cardiac chambers, abnormal heart looping, disruption of atrioventricular cushion formation, heart edema, and blood regurgitation. PAQR11 knockdown markedly reduces the number and proliferation rate of cardiomyocytes and alters the morphology of myocardial cells during early heart development. The cardiac defects caused by PAQR11 knockdown can be phenocopied by MEK inhibitors and a dominant negative Ras. Furthermore, constitutively active Ras and especially a Golgi-localized but not a plasma membrane–localized Ras are able to rescue the cardiac defects caused by PAQR11 knockdown.

Conclusion—This study not only provides in vivo evidence that PAQR11 plays a critical role in heart morphogenesis but also pinpoints the importance of compartmentalized Ras signaling during development.