PLoS Genetics (Apr 2020)

O-linked β-N-acetylglucosamine transferase plays an essential role in heart development through regulating angiopoietin-1.

  • Yongxin Mu,
  • Houzhi Yu,
  • Tongbin Wu,
  • Jianlin Zhang,
  • Sylvia M Evans,
  • Ju Chen

DOI
https://doi.org/10.1371/journal.pgen.1008730
Journal volume & issue
Vol. 16, no. 4
p. e1008730

Abstract

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O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only enzyme catalyzing O-GlcNAcylation. Although it has been shown that OGT plays an essential role in maintaining postnatal heart function, its role in heart development remains unknown. Here we showed that loss of OGT in early fetal cardiomyocytes led to multiple heart developmental defects including hypertrabeculation, biventricular dilation, atrial septal defects, ventricular septal defects, and defects in coronary vessel development. In addition, RNA sequencing revealed that Angiopoietin-1, required within cardiomyocytes for both myocardial and coronary vessel development, was dramatically downregulated in cardiomyocyte-specific OGT knockout mouse hearts. In conclusion, our data demonstrated that OGT plays an essential role in regulating heart development through activating expression of cardiomyocyte Angiopoietin-1.