Sphingosine 1-phosphate receptor-1 in cardiomyocytes is required for normal cardiac development

These results suggest that Sphingosine 1-phosphate signaling via S1P1 in cardiomyocytes plays a previously unknown and necessary role in heart development in mice

Hilary Clay; Lisa D. Wilsbacher; Stephen J. Wilson; Daniel N. Duong; Maayan McDonald; Ian Lam; Kitae Eric Park; Jerold Chun; Shaun R. Coughlin

2016

Scholarcy highlights

  • Sphingosine 1-phosphate is a bioactive lipid that acts via five G protein-coupled receptors called S1P1-S1P5
  • At face value, the temporal and spatial pattern of β-galactosidase staining seen in hearts from S1pr1+/LacZ embryos suggests that S1pr1 is expressed in most ventricular cardiomyocytes beginning at 9.5 dpc, is localized in the septum and trabecular myocardium at 12.5 and 14.5 dpc, and extends at lower levels into the inner compact myocardium as development proceeds
  • Our results demonstrate an unexpected role for S1pr1 in cardiomyocytes in heart development in mice
  • Loss of S1P1 in cardiomyocytes led to postnatal lethality, ventricular septal defects, and ventricular noncompaction
  • Loss of S1P1 appears to affect the process of compaction by an overall reduction in trabecular and compact layer cardiomyocyte number after 12.5 dpc
  • Compaction begins at ~12.5 dpc, with compact layer cardiomyocytes maintaining a higher proliferative rate than trabecular myocardium until the compact layer comprises the majority of ventricular mass
  • Disruption of endocardial and myocardial Notch signaling pathways after the onset of compaction leads to ventricular noncompaction, but in contrast to cardiomyocyte-specific S1pr1 deletion, these mutants display increased proliferation especially within the trabecular myocardium

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