title: Distinct roles for cell-autonomous Notch signaling in cardiomyocytes of the embryonic and adult heart.
abstract: BACKGROUND
  The Notch signaling pathway is important for cell-cell communication that controls tissue formation and homeostasis during embryonic and adult life, but the precise cell targets of Notch signaling in the mammalian heart remain poorly defined.
  
  
  OBJECTIVE
  To investigate the functional role of Notch signaling in the cardiomyocyte compartment of the embryonic and adult heart.
  
  
  RESULTS
  Here, we report that either conditional overexpression of Notch1 intracellular domain (NICD1) or selective silencing of Notch signaling in the embryonic cardiomyocyte compartment results in developmental defects and perinatal lethality. In contrast, augmentation of endogenous Notch reactivation after myocardial infarction in the adult, either by inducing cardiomyocyte-specific Notch1 transgene expression or by intramyocardial delivery of a Notch1 pseudoligand, increases survival rate, improves cardiac functional performance, and minimizes fibrosis, promoting antiapoptotic and angiogenic mechanisms.
  
  
  CONCLUSIONS
  These results reveal a strict requirement for cell-autonomous modulation of Notch signaling during heart morphogenesis, and illustrate how the same signaling pathway that promotes congenital heart defects when perturbed in the embryo can be therapeutically redeployed for the treatment of adult myocardial damage.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, Campus A. Buzzati-Traverso, Rome, Italy.
authors.forename: Paschalis
authors.initials: P
authors.lastname: Kratsios
authors.forename: Catarina
authors.initials: C
authors.lastname: Catela
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Salimova
authors.forename: Marion
authors.initials: M
authors.lastname: Huth
authors.forename: Valeria
authors.initials: V
authors.lastname: Berno
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Foteini
authors.initials: F
authors.lastname: Mourkioti
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation; D003097:Collateral Circulation / Q000502:physiology; D005318:Fetal Heart / Q000166:cytology; D005786:Gene Expression Regulation; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000502:physiology*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012038:Regeneration; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: C486455:Maml1 protein, mouse; C497762:Notch1 protein, mouse; D009687:Nuclear Proteins; D051881:Receptor, Notch1; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors