title: Progesterone and adipoQ receptor 11 links ras signaling to cardiac development in zebrafish.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors: Heng
authors: H
authors: Huang
authors: Ting
authors: T
authors: Jin
authors: Jing
authors: J
authors: He
authors: Qiurong
authors: Q
authors: Ding
authors: Daqian
authors: D
authors: Xu
authors: Lingdi
authors: L
authors: Wang
authors: Yixuan
authors: Y
authors: Zhang
authors: Yi
authors: Y
authors: Pan
authors: Zhenzhen
authors: Z
authors: Wang
authors: Yan
authors: Y
authors: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D048430:Cell Shape; D003001:Cloning, Molecular; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D009024:Morphogenesis; D060172:Morpholinos / Q000008:administration & dosage; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008164:Luminescent Proteins; D060172:Morpholinos; D047428:Protein Kinase Inhibitors; D054419:Receptors, Adiponectin; D011980:Receptors, Progesterone; D029961:Zebrafish Proteins; C575878:mmd protein, zebrafish; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins