Noncanonical Notch signals have opposing roles during cardiac development

Matthew Miyamoto, Peter Andersen, Edrick Sulistio, Xihe Liu, Sean Murphy, Suraj Kannan, Lucy Nam, William Miyamoto, Emmanouil Tampakakis, Narutoshi Hibino, Hideki Uosaki, Chulan Kwon

Research output: Contribution to journalArticlepeer-review


The Notch pathway is an ancient intercellular signaling system with crucial roles in numerous cell-fate decision processes across species. While the canonical pathway is activated by ligand-induced cleavage and nuclear localization of membrane-bound Notch, Notch can also exert its activity in a ligand/transcription-independent fashion, which is conserved in Drosophila, Xenopus, and mammals. However, the noncanonical role remains poorly understood in in vivo processes. Here we show that increased levels of the Notch intracellular domain (NICD) in the early mesoderm inhibit heart development, potentially through impaired induction of the second heart field (SHF), independently of the transcriptional effector RBP-J. Similarly, inhibiting Notch cleavage, shown to increase noncanonical Notch activity, suppressed SHF induction in embryonic stem cell (ESC)-derived mesodermal cells. In contrast, NICD overexpression in late cardiac progenitor cells lacking RBP-J resulted in an increase in heart size. Our study suggests that noncanonical Notch signaling has stage-specific roles during cardiac development.

Original languageEnglish (US)
Pages (from-to)12-16
Number of pages5
JournalBiochemical and Biophysical Research Communications
StatePublished - Nov 5 2021


  • Heart development
  • Noncanonical Notch signaling
  • Notch signaling
  • Second heart field

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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