Noncanonical Notch signals have opposing roles during cardiac development
| Autor: | Suraj Kannan, Hideki Uosaki, Peter Andersen, William Miyamoto, Xihe Liu, Matthew Miyamoto, Sean Murphy, Emmanouil Tampakakis, Edrick Sulistio, Narutoshi Hibino, Lucy Nam, Chulan Kwon |
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| Rok vydání: | 2021 |
| Předmět: |
Mesoderm
Biophysics Notch signaling pathway Xenopus Mice Transgenic Biology Biochemistry Article Mice medicine Animals Molecular Biology Cells Cultured Homeodomain Proteins Mice Knockout Receptors Notch Heart development Effector Myocardium Cell Differentiation Heart Mouse Embryonic Stem Cells Cell Biology biology.organism_classification Embryonic stem cell GATA4 Transcription Factor Cell biology medicine.anatomical_structure Immunoglobulin J Recombination Signal Sequence-Binding Protein Homeobox Protein Nkx-2.5 T-Box Domain Proteins Nuclear localization sequence Intracellular Signal Transduction Transcription Factors |
| Zdroj: | Biochem Biophys Res Commun |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.08.094 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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