Biochemical and biophysical research communications, 2021-11, Vol.577, p.12-16
2021
Details
- Autor(en) / Beteiligte
- Titel
- Noncanonical Notch signals have opposing roles during cardiac development
- Ist Teil von
- Biochemical and biophysical research communications, 2021-11, Vol.577, p.12-16
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •Noncanonical Notch signals play stage-specific roles during heart development.•Activation of noncanonical Notch inhibits heart formation in early development.•Second heart field formation is disrupted in noncanonical notch activated embryos.•Activation of noncanonical Notch in cardiomyocytes increases heart size.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2021.08.094Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8484041
- Format
- –
- Schlagworte
- Animals, Cell Differentiation, Cells, Cultured, GATA4 Transcription Factor - genetics, GATA4 Transcription Factor - metabolism, Heart - embryology, Heart development, Homeobox Protein Nkx-2.5 - genetics, Homeobox Protein Nkx-2.5 - metabolism, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics, Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism, Mesoderm - cytology, Mesoderm - embryology, Mesoderm - metabolism, Mice, Mice, Knockout, Mice, Transgenic, Mouse Embryonic Stem Cells - cytology, Mouse Embryonic Stem Cells - metabolism, Myocardium - cytology, Myocardium - metabolism, Noncanonical Notch signaling, Notch signaling, Receptors, Notch - metabolism, Second heart field, Signal Transduction, T-Box Domain Proteins - genetics, T-Box Domain Proteins - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism